Vaccines doi: 10.3390/vaccines12030324
Authors: Sochanwattey Meas Khuanjit Chaimongkolnukul Jaraspim Narkpuk Phenjun Mekvichitsaeng Kanokwan Poomputsa Nanchaya Wanasen Yaowaluck Maprang Roshorm
Porcine circovirus type 2 (PCV2) is the main causative agent of porcine circovirus-associated disease (PCVAD) that profoundly impacts the swine industry worldwide. While most of the commercial PCV vaccines are developed based on PCV genotype 2a (PCV2a), PCV genotype 2b (PCV2b) has become predominant since 2003. In this study, we developed and evaluated DNA-based bivalent vaccines covering both PCV2a and PCV2b. We generated a new immunogen, PCV2b-2a, by combining consensus sequences of the PCV2a and PCV2b capsid proteins (Cap2a and Cap2b) in a form of fusion protein. We also examined whether modifications of the PCV2b-2a fusion protein with a signal sequence (SS) and granulocyte macrophage-colony stimulating factor (GM-CSF) fusing with interleukine-4 (IL-4) (GI) could further improve the vaccine immunogenicity. An immunogenicity study of BALB/cAJcl mice revealed that the DNA vector pVAX1 co-expressing PCV2b-2a and GI (pVAX1.PCV2b-2a-GI) was most potent at inducing both antibody and cellular immune responses against Cap2a and Cap2b. Interestingly, the vaccines skewed the immune response towards Th1 phenotype (IgG2a > IgG1). By performing ELISA and ELISpot with predicted epitope peptides, the three most immunogenic B cell epitopes and five putative T cell epitopes were identified on Cap2a and Cap2b. Importantly, our DNA vaccines elicited broad immune responses recognizing both genotype-specific and PCV2-conserved epitopes. Sera from mice immunized with the DNAs expressing PCV2b-2a and PCV2b-2a-GI significantly inhibited PCV2a cell entry at serum dilution 1:8. All these results suggest a great potential of our PCV2b-2a-based vaccines, which can be further developed for use in other vaccine platforms to achieve both vaccine efficacy and economical production cost.
]]>Vaccines doi: 10.3390/vaccines12030323
Authors: Mia Ann Xu Jasmin Choi Joshua G. Rosenberger Rick S. Zimmerman Ralph DiClemente
African American men who have sex with men (MSM) are disproportionately impacted by HIV and may benefit from the development of an HIV vaccine. African American MSM are adversely affected by discrimination as a function of both their race and sexual behaviors. This may further increase the challenges associated with persuading them to adopt an HIV vaccine. Developing a knowledge base characterizing African American MSM HIV vaccine perceptions, attitudes, and concerns may help strengthen how healthcare providers and other health stakeholders describe and discuss the advent of an HIV vaccine. This study assessed the knowledge, attitudes, beliefs, and intentions related to HIV vaccination among African American MSM. This study comprised 432 African American MSM, 18–64 years, residing in the United States. Vaccine intention was defined as how likely it is that an individual would adopt an HIV vaccine if a vaccine was available and it was 90% effective against HIV, easy to obtain, free, and had few side effects. Relative to African American MSM who intend to delay receiving an HIV vaccination, controlling for age, education, and income, early vaccine adopters who had received ≥ 2 COVID-19 vaccinations and who had high WHO HIV Vaccine Positive Attitude Scale scores were, respectively, 3.2 times and 2.4 times more likely to report the intention to vaccinate within one year. Early vaccine adopters were also 2.4 times more likely to feel that HIV prevention support discriminates against African American MSM. Those reporting three or more sexual partners and medical mistrust were, respectively, 60% and 59% more likely to report the intention to delay HIV vaccination. The lack of a knowledge base on HIV vaccine perceptions and acceptability is a missed opportunity to provide guidance on how stakeholders, such as health providers and policymakers, should address HIV vaccine hesitancy once this crucial vaccine is licensed. The key factors affecting vaccine adoption are valuable in developing and implementing campaigns to enhance the HIV vaccine coverage in this vulnerable population.
]]>Vaccines doi: 10.3390/vaccines12030321
Authors: Xiaoyu Li Zengqiang Kou Ti Liu Wenjue An Wenqi An Wei Zhang Ke Zhang Jie Dong Jiangxuan Yu Yaqi Li Chenyan Zhao
This study explored the optimum immunization schedule for the quadrivalent influenza split-virion vaccine containing influenza A strains (H1N1 and H3N2) and B lineage strains (Yamagata and Victoria) in children aged 3–8 years. The 652 participants enrolled were divided into two groups based on a history of influenza immunization (IH group) or no history of influenza immunization (NH group). The groups were administered a two-dose immunization schedule on days 0 and 30. In the NH group, on day 30 after the first dose, the positive rates of influenza hemagglutination-inhibition antibodies of strains H1N1, H3N2, BV, and BY were 85.85%, 71.70%, 65.27% and 60.45%, respectively. The positive rates of BV and BY failed to meet the absolute criteria for evaluating the immunogenicity of influenza vaccine in the population aged 3–60 years (for each strain antibody). On day 30 after the second dose, HI antibodies to strains H1N1, H3N2, BV, and BY met the immunogenicity acceptable criteria. In the IH group, on day 30 after the first dose, HI antibodies to strains H1N1, H3N2, BV, and BY met the acceptable criteria for immunogenicity. The incidence rates of adverse reactions (vaccine-related adverse events) from the first dose up until 30 days after the second dose were 20.80% in the IH group and 19.50% in the NH group. Only two Grade 3 adverse reactions (fever: temperature ≥ 39.5 °C, swelling: area ≥ 50% of the injection site area) occurred in the IH group, and no Grade 3 adverse reactions occurred in the NH group. No serious adverse reactions occurred in either group. We conclude that for the NH group, two doses of quadrivalent influenza vaccine should be administered, and for the IH group, a one-dose regimen is acceptable.
]]>Vaccines doi: 10.3390/vaccines12030322
Authors: Paul E. Harris Scott Burkholz Charles V. Herst Reid M. Rubsamen
The Marburg virus (MARV), the virus responsible for Marburg hemorrhagic fever (MHF), is considered a top-priority pathogen for vaccine development. Recent outbreaks in Equatorial Africa have highlighted the urgency of MARV because of its high fatality rate and historical concerns about potential weaponization. Currently, there are no licensed vaccines for MARV. Existing vaccine candidates rely on attenuated recombinant vesicular stomatitis virus carrying MARV glycoprotein (VSVΔG) or the chimpanzee replication-defective adenovirus 3 vector ChAd3-MARV. Although these platforms provide significant protection in animal models, they face challenges because of their limited thermal stability and the need for cold storage during deployment in resource-poor areas. An alternative approach involves using adjuvanted poly (lactic-co-glycolic acid) (PLGA) microparticles loaded with synthetic peptides representing MHC class I—restricted T cell epitopes. This vaccine platform has demonstrated effectiveness in protecting against SARS-CoV-2 and EBoV disease in animal models and has the advantage of not requiring cold storage and remaining stable at room temperature for over six months. This report outlines the design, manufacturing, and in vivo immunogenicity testing of PLGA microparticle human vaccines designed to prevent Marburg hemorrhagic fever.
]]>Vaccines doi: 10.3390/vaccines12030320
Authors: Anirban Sengupta Noha Al-Otaibi Claudia Devito Francisca Lottersberger Jorma Hinkula
Currently, vaccine development against different respiratory diseases is at its peak. It is of utmost importance to find suitajble adjuvants that can increase the potency of the vaccine candidates. This study aimed to determine the systemic and splenic immune mechanisms in mice models induced by anionic and cationic lipid adjuvants in the presence of the vaccine-candidate influenza antigen hemagglutinin (HA). In the presence of the HA antigen, the cationic adjuvant (N3) increased conventional dendritic cell 1 (cDC1) abundance with enhanced MHCI and CD80-CD86 costimulatory marker expression, and significantly higher CD8T and Th17 populations with enhanced interferon-gamma (IFNγ) expression in CD8T and CD4T populations. Conversely, the anionic adjuvant (L3) increased the cDC2 population percentage with significantly higher MHCII and DEC205 expression, along with an increase in the CD4T and regulatory T cell populations. The L3-treated group also exhibited higher percentages of activated B and plasma cell populations with significantly higher antigen-specific IgG and IgA titer and virus neutralization potential. While the anionic adjuvant induced significantly higher humoral responses than the cationic adjuvant, the latter influenced a significantly higher Th1/Th17 response. For customized vaccine development, it is beneficial to have alternative adjuvants that can generate differential immune responses with the same vaccine candidate antigen. This study will aid the selection of adjuvants based on their charges to improve specific immune response arms in the future development of vaccine formulation.
]]>Vaccines doi: 10.3390/vaccines12030319
Authors: Şeyma Karatekin Selda Hançerli Törün Ebru Şenol Salih Çağrı Çakır Gülbin Gökçay
Pertussis is an important cause of mortality and morbidity in infancy. It is recommended that close contacts of the baby be vaccinated with Tdap, and this practice is called the cocoon strategy. This study aimed to investigate the applicability of the cocoon strategy and to determine the factors affecting the process. Mothers of babies who were hospitalized in the neonatal intensive care unit were included in the study. In the first stage, a face-to-face questionnaire was given to the mothers to measure their level of knowledge about whooping cough and its vaccine. In the second stage, written and verbal information about the cocoon strategy was given, and then vaccination intentions for Tdap were learned. In the third stage, all mothers were contacted 3 weeks after and asked whether they had received a Tdap vaccination and why. Of these mothers, 68% could not answer any questions about pertussis disease and vaccines correctly. After the information, 35% (n = 78) of the mothers stated that they were considering getting vaccinated, while only 2% (n = 5) of the mothers were able to get the Tdap vaccine. The most important reasons for not getting vaccinated were a lack of time (24%) and the cost of vaccination (23%). It is predicted that Tdap vaccination rates may increase if the cost of vaccine, availability of vaccine, and the access of mothers to the vaccine application are facilitated.
]]>Vaccines doi: 10.3390/vaccines12030318
Authors: Noelia Silva-Pilipich Uxue Beloki Laura Salaberry Cristian Smerdou
SARS-CoV-2 virus, the causative agent of COVID-19, has produced the largest pandemic in the 21st century, becoming a very serious health problem worldwide. To prevent COVID-19 disease and infection, a large number of vaccines have been developed and approved in record time, including new vaccines based on mRNA encapsulated in lipid nanoparticles. While mRNA-based vaccines have proven to be safe and effective, they are more expensive to produce compared to conventional vaccines. A special type of mRNA vaccine is based on self-amplifying RNA (saRNA) derived from the genome of RNA viruses, mainly alphaviruses. These saRNAs encode a viral replicase in addition to the antigen, usually the SARS-CoV-2 spike protein. The replicase can amplify the saRNA in transfected cells, potentially reducing the amount of RNA needed for vaccination and promoting interferon I responses that can enhance adaptive immunity. Preclinical studies with saRNA-based COVID-19 vaccines in diverse animal models have demonstrated the induction of robust protective immune responses, similar to conventional mRNA but at lower doses. Initial clinical trials have confirmed the safety and immunogenicity of saRNA-based vaccines in individuals that had previously received authorized COVID-19 vaccines. These findings have led to the recent approval of two of these vaccines by the national drug agencies of India and Japan, underscoring the promising potential of this technology.
]]>Vaccines doi: 10.3390/vaccines12030317
Authors: Miriam Capasso Marcella Bianchi Daniela Caso
Vaccine hesitancy poses a significant threat to the health of individuals across all age groups, which has been exacerbated by the COVID-19 pandemic. In this cross-sectional study, an extension of the Theory of Planned Behavior (TPB) was applied to investigate psychosocial variables predicting intention to vaccinate children under 12 against COVID-19 in a sample of 420 Italian parents (Mean age = 40.4, SD = 5.9; Women = 78.1%). Hierarchical regression analysis revealed that, among the TPB variables, cognitive attitude, descriptive norms, and perceived behavioral control significantly predicted parents’ vaccination intention. Furthermore, including trust in the institutions’ ability to manage the vaccination campaign in the model significantly increased the explained variance in intention. These findings suggest that campaigns promoting childhood COVID-19 vaccination should not only emphasize the safety and effectiveness of vaccines for children but also focus on reducing barriers to vaccination. Additionally, attention should be given to enhancing the perception that this behavior is widespread among other parents, thus leveraging the power of social influence. Finally, and not less important, significant efforts should be directed toward building and reinforcing trust in the system of actors promoting and managing the COVID-19 vaccination campaign.
]]>Vaccines doi: 10.3390/vaccines12030316
Authors: Nilanshu Manocha Daphné Laubreton Xavier Robert Jacqueline Marvel Virginie Gueguen-Chaignon Patrice Gouet Prashant Kumar Madhu Khanna
Dengue virus (DENV) infection continues to be a public health challenge, lacking a specific cure. Vaccination remains the primary strategy against dengue; however, existing live-attenuated vaccines display variable efficacy across four serotypes, influenced by host serostatus and age, and predominantly inducing humoral responses. To address this limitation, this study investigates a multiepitope-based immunogen designed to induce robust cellular immunity across all DENV serotypes. The chimeric immunogen integrates H-2d specific MHC-I binding T-cell epitopes derived from conserved domains within the DENV envelope protein. Immuno-informatics analyses supported its stability, non-allergenic nature, and strong MHC-I binding affinity as an antigen. To assess the immunogenicity of the multiepitope, it was expressed in murine bone-marrow-derived dendritic cells (BMDCs) that were used to prime mice. In this experimental model, simultaneous exposure to T-cell epitopes from all four DENV serotypes initiated distinct IFNγ-CD8 T-cell responses for different serotypes. These results supported the potential of the multiepitope construct as a vaccine candidate. While the optimization of the immunogen design remains a continuous pursuit, this proof-of-concept study provides a starting point for evaluating its protective efficacy against dengue infection in vivo. Moreover, our results support the development of a multiepitope vaccine that could trigger a pan-serotype anti-dengue CD8 response.
]]>Vaccines doi: 10.3390/vaccines12030315
Authors: Giacomo Biganzoli Marco Mendola Pier Mario Perrone Laura Maria Antonangeli Anna Beatrice Elena Longo Paolo Carrer Claudio Colosio Dario Consonni Giuseppe Marano Patrizia Boracchi Elia Biganzoli Silvana Castaldi
Background: COVID-19 vaccination is the most significant step toward the long-term mitigation of SARS-CoV-2-related complication, avoiding disease and death and decreasing virus spread. This study aimed to evaluate, in a real-world setting, booster dose effectiveness to reduce COVID-19 risk considering the amount of time after the end of the two-dose vaccination cycle. A sub-analysis was conducted to adjust the booster dose effect for occupational and demographic factors. Methods: About 16,000 COVID-19-vaccinated HCWs of three University Hospital Networks in Milan (HN1/HN2/HN3) were included in the study. Data were collected by Occupational Health Physicians of the HNs within specific computerized databases. Results: In univariable analysis, booster dose administration displayed a slightly higher risk of infection with respect to not receiving it, OR = 1.18, with 95% confidence interval (C.I) [0.99, 1.41]. When the model was adjusted with the modulating effect of time from the completion of the vaccination cycle on booster dose administration, the latter resulted in strong protective effect against infection, OR = 0.43, 95% CI [0.26, 0.74]. However, considering the modifying influence of time from the vaccination cycle’s completion, the administration of booster doses appeared to have a protective effect against infection. In HN1, students and resident physicians displayed lower odds of infection with respect to physicians. Lastly, a non-linear effect of age was reported. Conclusions: Our findings suggest that the correct timing in vaccine scheduling and administration is critical to vaccine effectiveness. These findings, applicable to all vaccinations, should help in setting up more effective vaccination strategies.
]]>Vaccines doi: 10.3390/vaccines12030314
Authors: Niket Thakkar Ali Haji Adam Abubakar Mukhtar Shube Mustafe Awil Jama Mohamed Derow Philipp Lambach Hossam Ashmony Muhammad Farid So Yoon Sim Patrick O’Connor Anna Minta Anindya Sekhar Bose Patience Musanhu Quamrul Hasan Naor Bar-Zeev Sk Md Mamunur Rahman Malik
Somalia is a complex and fragile setting with a demonstrated potential for disruptive, high-burden measles outbreaks. In response, since 2018, Somalian authorities have partnered with UNICEF and the WHO to implement measles vaccination campaigns across the country. In this paper, we create a Somalia-specific model of measles transmission based on a comprehensive epidemiological dataset including case-based surveillance, vaccine registries, and serological surveys. We use this model to assess the impact of these campaign interventions on Somalian’s measles susceptibility, showing, for example, that across the roughly 10 million doses delivered, 1 of every 5 immunized a susceptible child. Finally, we use the model to explore a counter-factual epidemiology without the 2019–2020 campaigns, and we estimate that those interventions prevented over 10,000 deaths.
]]>Vaccines doi: 10.3390/vaccines12030313
Authors: Alexander J. Badten Alfredo G. Torres
Burkholderia are a group of Gram-negative bacteria that can cause a variety of diseases in at-risk populations. B. pseudomallei and B. mallei, the etiological agents of melioidosis and glanders, respectively, are the two clinically relevant members of the B. pseudomallei complex (Bpc). The development of vaccines against Bpc species has been accelerated in recent years, resulting in numerous promising subunits and glycoconjugate vaccines incorporating a variety of antigens. However, a second group of pathogenic Burkholderia species exists known as the Burkholderia cepacia complex (Bcc), a group of opportunistic bacteria which tend to affect individuals with weakened immunity or cystic fibrosis. To date, there have been few attempts to develop vaccines to Bcc species. Therefore, the primary goal of this review is to provide a broad overview of the various subunit antigens that have been tested in Bpc species, their protective efficacy, study limitations, and known or suspected mechanisms of protection. Then, we assess the reviewed Bpc antigens for their amino acid sequence conservation to homologous proteins found in Bcc species. We propose that protective Bpc antigens with a high degree of Bpc-to-Bcc sequence conservation could serve as components of a pan-Burkholderia vaccine capable of protecting against both disease-causing groups.
]]>Vaccines doi: 10.3390/vaccines12030312
Authors: Wei-Chun Chen Shu-Yu Hu Chao-Min Cheng Ching-Fen Shen Hui-Yu Chuang Chin-Ru Ker Der-Ji Sun Ching-Ju Shen
This study assessed IgG levels to influenza/pertussis and neutralizing antibody (Nab) responses of COVID-19 vaccines in blood of pregnant women following immunization with pertussis (Tdap), influenza, and COVID-19 vaccines. We prospectively collected 71 participants categorized by the following vaccine combinations: 3TI, 4TI, 3T, and 4T groups (three and four doses of COVID-19 vaccines plus Tdap/influenza or Tdap vaccines alone). Our findings have indicated that the 3TI group exhibited elevated IgG levels for influenza B compared to the 3T group (12.90 vs. 7.75 U, p = 0.001); this pattern was not observed for influenza A. Pertussis IgG levels remained uniform across all groups. The 4TI group demonstrated a greater Nab inhibition rate from COVID-19 vaccines compared to both the 3TI and 3T groups (61.34% vs. 22.5% and 15.16%, respectively, p = 0.001). We observed no correlation between Nab inhibition rate and IgG levels for Tdap/influenza, with the exception of a moderate correlation with influenza B in the 3TI group. The efficacy of Tdap vaccine in pregnant women remained consistent, regardless of the administration of COVID-19 or influenza vaccines. Interestingly, without the influenza vaccine, both three and four doses of the COVID-19 vaccine still offered protection against influenza A, but not B. Hence, co-administering COVID-19, influenza, and Tdap vaccines during prenatal care maintains immunogenicity and is highly advised to safeguard pregnant women fully.
]]>Vaccines doi: 10.3390/vaccines12030311
Authors: Suha Ali Batarfi Rosnah Sutan Halim Ismail Abdulla Salem Bin-Ghouth
Although immunization is one of the most successful and cost-effective interventions that prevents millions of infant and child deaths yearly, it has failed to achieve its intended goals in some low-income countries. Yemen is currently experiencing the most extreme humanitarian crisis globally, which has affected health and worsened its economy and political governance instability. There are few reports on Yemeni vaccination statuses. The present study aimed to investigate the effect of the public health emergency crises on childhood immunization in Yemen. A retrospective descriptive study was conducted in the Coastal Hadhramaut Governorate, Yemen. Secondary data from governorate annual reports for 2013–2020 were extracted. The assessment of the annual immunization coverage rate according to each vaccine was tabulated. The analysis revealed that the 2013–2019 vaccination coverage in Coastal Hadhramaut demonstrated an increasing trend. However, vaccination coverage decreased for all vaccines in 2015–2016 and 2020. Although all three doses of the pentavalent vaccine demonstrated >85% coverage in all years, the coverage of the first and second doses decreased in 2016, and the coverage of all doses decreased in 2020 during the COVID-19 pandemic. Public health emergencies negatively affected routine immunization coverage in Yemen. The trend correlated with the humanitarian crisis and other research findings in Yemen. The national response to public health threats during emergency crises must involve strengthening the program for monitoring and evaluating vaccine-preventable diseases.
]]>Vaccines doi: 10.3390/vaccines12030310
Authors: Francys Avendaño-Rangel Gabriela Agra-Duarte Pedro B. Borba Valdomiro Moitinho Leslye T. Avila Larissa O. da Silva Sayonara M. Viana Rohit Sharma Sreenivas Gannavaram Hira L. Nakhasi Camila I. de Oliveira
Immunization with various Leishmania species lacking centrin induces robust immunity against a homologous and heterologous virulent challenge, making centrin mutants a putative candidate for a leishmaniasis vaccine. Centrin is a calcium-binding cytoskeletal protein involved in centrosome duplication in higher eukaryotes and Leishmania spp. lacking centrin are unable to replicate in vivo and are non-pathogenic. We developed a centrin-deficient Leishmania braziliensis (LbCen−/−) cell line and confirmed its impaired survival following phagocytosis by macrophages. Upon experimental inoculation into BALB/c mice, LbCen−/− failed to induce lesions and parasites were rapidly eliminated. The immune response following inoculation with LbCen−/− was characterized by a mixed IFN-γ, IL-4, and IL-10 response and did not confer protection against L. braziliensis infection, distinct from L. major, L. donovani, and L mexicana centrin-deficient mutants. A prime-boost strategy also did not lead to a protective immune response against homologous challenge. On the contrary, immunization with centrin-deficient L. donovani (LdonCen−/−) cross-protected against L. braziliensis challenge, illustrating the ability of LdonCen−/− to induce the Th1-dominant protective immunity needed for leishmaniasis control. In conclusion, while centrin deficiency in L. braziliensis causes attenuation of virulence, and disrupts the ability to cause disease, it fails to stimulate a protective immune response.
]]>Vaccines doi: 10.3390/vaccines12030309
Authors: Rebeca M. Santamaria Karel Estrada María E. López Edith Rojas Grecia Martínez Yazmín Alcalá Carmen Rojas Jesús Antonio Álvarez José J. Lira Tomás V. Santamaria Alejandro Sánchez-Flores Julio V. Figueroa
Bovine babesiosis, caused by the protozoan Babesia bigemina, is one of the most important hemoparasite diseases of cattle in Mexico and the world. An attenuated B. bigemina strain maintained under in vitro culture conditions has been used as a live attenuated vaccine; however, the biological mechanisms involved in attenuation are unknown. The objective of this study was to identify, through a comparative transcriptomics approach, the components of the B. bigemina virulent parasites that are differentially expressed in vivo, as opposed to those expressed by B. bigemina attenuated vaccine parasites when inoculated into naïve cattle. The biological material under study was obtained by inoculating spleen-intact cattle with infected erythrocytes containing either the attenuated strain or a virulent field strain. After RNA extraction, transcriptomic analysis (RNA-seq) was performed, followed by bioinformatic Differential Expression (DE) analysis and Gene Ontology (GO) term enrichment. The high-throughput sequencing results obtained by analyzing three biological replicates for each parasite strain ranged from 9,504,000 to 9,656,000, and 13,400,000 to 15,750,000 reads for the B. bigemina attenuated and virulent strains, respectively. At least 519 differentially expressed genes were identified in the analyzed strains. In addition, GO analysis revealed both similarities and differences across the three categories: cellular components, biological processes, and molecular functions. The attenuated strain of B. bigemina derived from in vitro culture presents global transcriptomic changes when compared to the virulent strain. Moreover, the obtained data provide insights into the potential molecular mechanisms associated with the attenuation or pathogenicity of each analyzed strain, offering molecular markers that might be associated with virulence or potential vaccine candidates.
]]>Vaccines doi: 10.3390/vaccines12030308
Authors: Bo-Hung Liao Louise Platen Myriam Grommes Cho-Chin Cheng Christopher Holzmann-Littig Catharina Christa Bernhard Haller Verena Kappler Romina Bester Maia Lucia Werz Eva Platen Peter Eggerer Laëtitia Tréguer Claudius Küchle Christoph Schmaderer Uwe Heemann Lutz Renders Ulrike Protzer Matthias Christoph Braunisch
Background: Hemodialysis patients have reduced serologic immunity after SARS-CoV-2 vaccination compared to the general population and an increased risk of morbidity and mortality when exposed to SARS-CoV-2. Methods: Sixty-six hemodialysis patients immunized four times with the original SARS-CoV-2 vaccines (BNT162b2, mRNA-1273) either received a booster with the adapted Comirnaty Original/Omicron BA.4-5 vaccine 8.3 months after the fourth vaccination and/or experienced a breakthrough infection. Two months before and four weeks after the fifth vaccination, the live-virus neutralization capacities of Omicron variants BA.5, BQ.1.1, and XBB.1.5 were determined, as well as neutralizing and quantitative anti-SARS-CoV-2 spike-specific IgG antibodies. Results: Four weeks after the fifth vaccination with the adapted vaccine, significantly increased neutralizing antibodies and the neutralization of Omicron variants BA.5, BQ.1.1, and XBB.1.5 were observed. The increase was significantly higher than after the fourth vaccination for variants BQ.1.1 and BA.5. Of all analyzed variants, BA.5 was neutralized best after the fifth vaccination. We did not see a difference in humoral immunity between the group with an infection and the group with a vaccination as a fifth spike exposure. Fivefold-vaccinated patients with a breakthrough infection showed a significantly higher neutralization capacity of XBB.1.5. Conclusion: A fifth SARS-CoV-2 vaccination with the adapted vaccine improves both wild-type specific antibody titers and the neutralizing capacity of the current Omicron variants BA.5, BQ.1.1, and XBB.1.5 in hemodialysis patients. Additional booster vaccinations with adapted vaccines will likely improve immunity towards current and original SARS-CoV-2 variants and are, therefore, recommended in hemodialysis patients. Further longitudinal studies must show the extent to which this booster vaccination avoids a breakthrough infection.
]]>Vaccines doi: 10.3390/vaccines12030307
Authors: Cristina Aira Gabriela González-García Juan Martínez-Cano Nuria de la Roja Monica Giammarioli Francesco Feliziani Žanete Šteingolde Jurate Buitkuviene Petr Václavek Dimitrije Glišić Carmina Gallardo Patricia Sastre Marga García-Durán Paloma Rueda Alba Fresco-Taboada
African swine fever (ASF) is a contagious disease of wild boar and domestic pigs notifiable to the World Organisation for Animal Health due to its high socio-economic impact. ASF is caused by the complex ASF virus (ASFV), and it can present different clinical manifestations that can be confused with other diseases; for this reason, laboratory testing is necessary for the proper diagnosis of clinically suspected animals. Despite the efforts put into it over decades, no treatment or safe vaccine is globally available, and disease control is based on early diagnosis and the implementation of strict biosecurity measures. In this context, rapid tests have the potential to accelerate and facilitate the identification of infected animals by giving fast on-site results. In this work, we improved the available point-of-care assays for the diagnosis of the disease by the development of a more specific antigen test and a more sensitive antibody test. This antibody detection test allowed for the earlier detection of infected animals than two commercial indirect ELISAs (statistically significant). Moreover, we developed a combined dual rapid test, unifying, in the same cassette, an antigen detection strip and an antibody detection strip. In this study, we confirmed that this combo approach is a useful tool for implementing rapid tests in the field since it increases the percentage of positive samples detected, even when PCR turns negative, while maintaining a good specificity.
]]>Vaccines doi: 10.3390/vaccines12030306
Authors: Elena Cecilia Rosca Almonzer Al-Qiami Amalia Cornea Mihaela Simu
Background: Parsonage–Turner syndrome (PTS) is an inflammatory condition of the brachial plexus, with more than half of patients presenting a trigger, such as infection or vaccination. Our objective was to synthesize the clinical and paraclinical features, therapeutic responses, and outcomes of PTS post-COVID-19 vaccination. Methods: We systematically reviewed two databases (LitCOVID and the WHO database on COVID-19) up to January 2024 following a published protocol (OSF registries). Results: We included 59 cases. PTS occurred more frequently in males (61.1% mRNA group, 83.3% viral vector group). Patients in the mRNA group were younger (41.7% between 41 and 50 years vs. 38.9% between 61 and 70 years). Most cases had sudden pain within two weeks. Unilateral PTS was present in 94.4% of mRNA and all viral vector-vaccinated cases. Symptoms included pain (97.1% and 92.3%, respectively), usually followed within two weeks by motor deficits (97.2% and 94.1%, respectively), amyotrophy (30% and 81.8%, respectively), paresthesia (50% and 27.3%, respectively), and sensory loss (33.3% and 38.5%, respectively). Viral vector vaccine recipients had nerve involvement outside the brachial plexus. Ancillary investigations revealed CSF albuminocytological dissociation (33.3% and 100%, respectively) and ipsilateral axillary lymphadenopathy. Two PTS cases worsened after the second mRNA dose, and another recurred after influenza vaccination. One patient well tolerated the second dose of the viral vector vaccine, but symptoms reemerged in another. Conclusions: Current evidence suggests PTS may occur after all COVID-19 vaccine types, with some subgroup differences. Also, PTS might recur with subsequent similar or unrelated vaccines.
]]>Vaccines doi: 10.3390/vaccines12030305
Authors: Claudio Costantino Walter Mazzucco Giorgio Graziano Carmelo Massimo Maida Francesco Vitale Fabio Tramuto
The current influenza season started in Italy in October 2023, approaching the epidemic peak in late December (52nd week of the year). We aimed to explore the mid-term virologic surveillance data of the 2023/2024 influenza season (from 16 October 2023 to 7 January 2024) in Sicily, the fourth most populous Italian region. A test-negative design was used to estimate the effectiveness of seasonal influenza vaccine (VE) against A(H1N1)pdm09 virus, the predominant subtype in Sicily (96.2% of laboratory-confirmed influenza cases). Overall, 29.2% (n = 359/1230) of oropharyngeal swabs collected from patients with influenza-like illness (ILI) were positive for influenza. Among the laboratory-confirmed influenza cases, 12.5% (n = 45/359) were vaccinated against influenza, with higher prevalence of laboratory-confirmed diagnosis of influenza A among subjects vaccinated with quadrivalent inactivated standard dose (29.4%), live attenuated intranasal (25.1%), and quadrivalent inactivated high-dose (23.8%) influenza vaccines. Comparing influenza vaccination status for the 2023/2024 season among laboratory-confirmed influenza-positive and -negative samples, higher vaccination rates in influenza-negative samples (vs. positive) were observed in all age groups, except for 45–64 years old, regardless of sex and comorbidities. The overall adjusted VE (adj-VE) was 41.4% [95%CI: 10.5–61.6%], whereas the adj-VE was 37.9% [95%CI: −0.7–61.7%] among children 7 months–14 years old and 52.7% [95%CI: −38.0–83.8%] among the elderly (≥65 years old).
]]>Vaccines doi: 10.3390/vaccines12030304
Authors: Jiangxu Yu Jiyang Fu Hongshuo Liu Chao Kang Zesong Wang Yancheng Jin Shuxuan Wu Tianzhi Li Ruicheng Yang Meilin Jin Huanchun Chen Xiangru Wang
Enterotoxigenic Escherichia coli (ETEC) causes severe diarrhea in piglets. The current primary approach for ETEC prevention and control relies on antibiotics, as few effective vaccines are available. Consequently, an urgent clinical demand exists for developing an effective vaccine to combat this disease. Here, we utilized food-grade Lactococcus lactis NZ3900 and expression plasmid pNZ8149 as live vectors, together with the secreted expression peptide Usp45 and the cell wall non-covalent linking motif LysM, to effectively present the mutant LTA subunit, the LTB subunit of heat-labile enterotoxin, and the FaeG of F4 pilus on the surface of recombinant lactic acid bacteria (LAB). Combining three recombinant LAB as a live vector oral vaccine, we assessed its efficacy in preventing F4+ ETEC infection. The results demonstrate that oral immunization conferred effective protection against F4+ ETEC infection in mice and piglets lacking maternal antibodies during weaning. Sow immunization during late pregnancy generated significantly elevated antibodies in colostrum, which protected piglets against F4+ ETEC infection during lactation. Moreover, booster immunization on piglets during lactation significantly enhanced their resistance to F4+ ETEC infection during the weaning stage. This study highlights the efficacy of an oral LAB vaccine in preventing F4+ ETEC infection in piglets by combining the sow immunization and booster immunization of piglets, providing a promising vaccination strategy for future prevention and control of ETEC-induced diarrhea in piglets.
]]>Vaccines doi: 10.3390/vaccines12030303
Authors: Hanna Carlsson Lars Brudin Lena Serrander Jorma Hinkula Ivar Tjernberg
Immunization against influenza through vaccination is the most effective method with which to prevent infection. To assess protection after immunization, analysing humoral response with a hemagglutinin inhibition assay is the gold standard, but cell-mediated immune response has been shown to better correlate with protection in the elderly. Our aim was to explore the influenza-specific cell-mediated and mucosal humoral responses in serologically defined responders and non-responders. We analysed sera for total immunoglobulins (Ig) A, G, and M and nasal swab samples for influenza-specific IgA. Peripheral blood mononuclear cells were stimulated with trivalent influenza vaccine VaxiGripTetra, and supernatants were analysed for influenza-specific responses with the Olink Immune-Oncology panel using a proximity extension assay. We included 73 individuals, of which 69 completed the study with follow-up sampling at one and six months post-vaccination. Of the 73, 51 (70%) were found to be serological responders and 22 (30%) were non-responders. We did not find any significant differences in sex or mucosal humoral response between responders and non-responders; however, a higher IFNγ/IL-10 ratio in individuals ≤65 years of age indicates an enhanced cell-mediated immune response in this age group. Characteristics of the non-responders were found to be higher levels of IgM, Granzyme B and Interleukin 12, and lower levels of C-X-C motif chemokine 13 compared with those of the responders. In conclusion, our results did not show any correlation between serological response and age. Furthermore, the majority of influenza-specific cell-mediated immune markers did not differ between responders and non-responders; the immune marker profile of the non-responders and its contribution to protection is of interest but needs to be further explored.
]]>Vaccines doi: 10.3390/vaccines12030302
Authors: Zohra Bamouh Amal Elarkam Soufiane Elmejdoub Jihane Hamdi Zineb Boumart Greg Smith Matthew Suderman Mahder Teffera Hezron Wesonga Stephen Wilson Douglas M. Watts Shawn Babiuk Brad Pickering Mehdi Elharrak
The use of effective vaccines is among the most important strategies for the prevention and progressive control of transboundary infectious animal diseases. However, the use of vaccine is often impeded by the cost, a lack of cold chains and other factors. In resource-limited countries in Africa, one approach to improve coverage and reduce cost is to vaccinate against multiple diseases using combined vaccines. Therefore, the objective of this study was to evaluate a combined vaccine for the prevention and control of Lumpy Skin Disease (LSD), Contagious Bovine Pleuropneumonia (CBPP) and Rift Valley fever (RVF). The LSD and CBPP were formulated as a combined vaccine, and the RVF was formulated separately as live attenuated vaccines. These consisted of a Mycoplasma MmmSC T1/44 strain that was propagated in Hayflick-modified medium, RVF virus vaccine, C13T strain prepared in African green monkey cells (Vero), and the LSDV Neethling vaccine strain prepared in primary testis cells. The vaccines were tested for safety via the subcutaneous route in both young calves and pregnant heifers with no side effect, abortion or teratogenicity. The vaccination of calves induced seroconversions for all three vaccines starting from day 7 post-vaccination (PV), with rates of 50% for LSD, 70% for CBPP and 100% for RVF, or rates similar to those obtained with monovalent vaccines. The challenge of cattle vaccinated with the LSD/CBPP and the RVF vaccine afforded full protection against virulent strains of LSDV and RVFV. A satisfactory level of protection against a CBPP challenge was observed, with 50% of protection at 6 months and 81% at 13 months PV. A mass vaccination trial was performed in four regions of Burkina Faso that confirmed safety and specific antibody responses induced by the vaccines. The multivalent LSD/CBPP+RVF vaccine provides a novel and beneficial approach to the control of the three diseases through one intervention and, therefore, reduces the cost and improves vaccination coverage.
]]>Vaccines doi: 10.3390/vaccines12030301
Authors: Hyunhye Kang Jin Jung Geon Young Ko Jihyun Lee Eun-Jee Oh
The immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) becomes increasingly complex as individuals receive different combinations of vaccine doses and encounter breakthrough infections. Our study focused on the immunogenicity observed over a two-year period in healthy individuals who completed a two-dose series and then experienced booster and/or Omicron infection. In June 2023, we recruited 78 healthcare workers who had previously participated in clinical research initiated in March 2021 at a single medical center in South Korea. At 1, 5, 11, and 25 months after a second dose, we assessed SARS-CoV-2–specific humoral and cellular immune responses. Longitudinal monitoring revealed a significant decline in humoral immunity levels after the second vaccine dose, followed by a substantial increase post-third vaccination or breakthrough infection. In contrast, stable cellular immune responses were consistently observed, with peak humoral and cellular immune measures reached at 25 months after the second dose. Among infection-naïve participants, three-dose vaccinated individuals had decreased neutralizing activity against wild-type (WT) and negative activities against Omicron subvariants BA.2 and BA.4/5, whereas those who received a fourth dose of bivalent BNT had significantly increased neutralizing activity (p < 0.05). All immune metrics tended to increase as the number of vaccine doses increased. Among participants with 4-exposure, homologous vaccination (mRNA × 4) led to higher humoral immunity, whereas heterologous vaccination (ChAd × 2/mRNA × 2) induced stronger cellular responses against multiple SARS-CoV-2 variants by enzyme-linked immunospot assays (p < 0.05). Immune responses from bivalent vaccines or Omicron infection did not show statistically significant differences among exposure number-matched participants (p > 0.05). Omicron exposure significantly increased cross-neutralizing activity, but magnitude of cellular immunity was not significantly altered by Omicron exposure. Our longitudinal study highlights the evolving complexity of SARS-CoV-2 immune responses, showing enhanced immunity with multiple vaccine doses and robust cellular responses from heterologous vaccination. These findings emphasize the need for ongoing surveillance to optimize vaccination strategies against emerging variants.
]]>Vaccines doi: 10.3390/vaccines12030300
Authors: Mingyang Li Mengyuan Liu Shaohui Song Ruirui Zhao Yun Xie Jing Liu Lilan Xu Xuefeng Ma Mingyu Song Jian Zhou Guoyang Liao
Vaccines are one of the most effective means of preventing influenza A, typically containing the hemagglutinin (HA) of the influenza A virus. However, antigenic drift and shift of the influenza A virus can lead to instability in vaccine efficacy. Compared to HA, the antigenic variation rate of neuraminidase (NA) is slower. In traditional inactivated influenza vaccines, although they contain a certain amount of NA, there are significant differences between different batches, which cannot consistently induce NA-based immune responses. Therefore, NA is often overlooked in vaccine development. In this study, we report an mRNA vaccine encoding the NA of two strains of influenza A virus. The experimental results demonstrated that when matched with the viral strain, this mRNA vaccine induced high levels of neutralizing antibodies, providing a protective effect to mice in viral challenge experiments, and this immune response was shown to be biased towards the Th1 type. In summary, this study demonstrates that NA is a promising potential antigen, providing new insights for the development of influenza A virus vaccines.
]]>Vaccines doi: 10.3390/vaccines12030299
Authors: Peter Priester Miroslav Fajfr Veronika Molnarova Radek Sleha Sylva Janovska Pavel Bostik Stanislav Filip
Aside from the general population, the COVID-19 pandemic has also affected a group of patients in palliative oncology care. In this study, long-term immune responses against SARS-CoV-2 after vaccination were monitored in a cohort of patients in palliative oncology care. This non-randomized, prospective, and open-label pilot study recruited patients from the Palliative Oncology Program and included 147 patients, of which 80 were females (54.4%) and 67 males (45.6%). The overall evaluation included current health status, SARS-CoV-2 anti-S IgG titer, and neutralizing antibodies using the SARS-CoV-2 virus neutralization test (VNT). Anti-S IgG antibody analysis revealed high (H) antibody levels in 35.7% (n = 10) and very high (VH) levels in 39.3% (n = 11) of patients after the second vaccination dose. Similarly, after the third dose, H was found in 29.6% (n = 32) and VH in 55.5% (n = 60) of patients. High and very high anti-S IgG antibody levels were consistent with high VNT titers (>2560) and H antibody levels in 17.1% (n = 12) or VH in 82.9% (n = 58) of patients. Patients with two or more doses showed H and VH antibody levels at a median of 451 and 342 days after vaccination, respectively. In this clinical trial, patients showed high and very high levels of anti-S IgG antibodies over a longer period of time. These patients did not show reduced immunological responses to the COVID-19 vaccine challenge. We can assume that prevention through vaccination can reduce the risk of complications or death from COVID-19 in patients in early palliative oncology care.
]]>Vaccines doi: 10.3390/vaccines12030298
Authors: Ferran Tarrés-Freixas Bonaventura Clotet Jorge Carrillo Julià Blanco
The development of HIV prophylactic vaccines is facing an impasse, since all phase IIb/III clinical trials were halted in 2023 without demonstrating efficacy. Thus, the field is in need of developing novel immunogens and vaccination strategies that induce broadly neutralising antibodies together with potent Fc-dependent effector functions, as well as protective cross-reactive CD4+ and CD8+ T cell responses. Nucleic acid vaccines, particularly mRNA vaccines, have been one of the major groundbreaking advances in the current decade. Nucleic acid vaccines may help recalibrate the HIV vaccine field towards the use of delivery systems that allow the proper expression of immunogens as a sole antigen (i.e., membrane-bound trimeric envelope glycoproteins) or even to be displayed in a multiantigen platform that will be synthesised by the host. In this review, we will summarise how the multiple HIV vaccine strategies pursued in the last 40 years of HIV research have driven current vaccine development, which are the most relevant immunogens identified so far to induce balanced adaptive immune responses, and how they can benefit from the acceptance of nucleic acid vaccines in the market by reducing the limitations of previous delivery systems. The incorporation of nucleic acid vaccines into the current heterogeneous repertoire of vaccine platforms may represent an invaluable opportunity to reignite the fight against HIV.
]]>Vaccines doi: 10.3390/vaccines12030297
Authors: Angelo Capodici Aurelia Salussolia Giusy La Fauci Zeno Di Valerio Marco Montalti Anna Odone Claudio Costantino Heidi J. Larson Julie Leask Jacopo Lenzi Lamberto Manzoli Davide Gori on behalf of the OBVIOUS Board on behalf of the OBVIOUS Board
Influenza is a significant public health concern, with Italy being profoundly impacted annually. Despite extensive vaccination campaigns and cooperative initiatives between the Public Health Departments of Local Healthcare Authorities and family physicians, low vaccine uptake rates persist. This study builds upon the OBVIOUS project, providing an updated picture of influenza vaccine uptake in Italy through a representative sample. A cross-sectional computer-assisted web interviewing (CAWI) survey of 10,001 Italian citizens was conducted between 31 March and 5 June 2023. Our findings underscore the negative impact of a lack of awareness that a person is in a priority group for influenza vaccination (−26.1 percentage points in vaccine uptake) and the profound influence of social circles on vaccination decisions (−5 percentage points when unfavorable). Medical professionals played a pivotal role, with recommendations from family doctors significantly promoting vaccine uptake (+20.2 percentage points). Age, chronic conditions, and socio-demographic factors also influenced vaccination behaviors. For children, parental negative perceptions regarding the flu (−10.4 percentage points) and vaccine safety (−23.4 percentage points) were crucial determinants. The present study emphasizes the need for a comprehensive approach addressing awareness, societal beliefs, and tailored medical advice to enhance vaccination rates and protect public health in Italy.
]]>Vaccines doi: 10.3390/vaccines12030296
Authors: Muriel Schraad Stefan Runkel Walter Hitzler Maria Protopapa Stefan Bittner Timo Uphaus Frauke Zipp
Immunomodulatory and immunosuppressive therapy is needed in people with a chronic neuroinflammatory disease of the central nervous system such as multiple sclerosis (MS). Therefore, MS requires monitoring for and preventing against infectious diseases like SARS-CoV-2. Vaccination and anti-viral treatments are, in particular, recommended for elderly people and people at risk of a severe course of infection and of MS. Here, we asked whether repetitive infection or vaccination influenced responses upon receiving high efficacy treatments, namely sphingosine-1-phosphate receptor modulator (S1P) or anti-CD20 B cell antibody (anti-CD20) treatments. We performed a prospective real-world study of people with MS (pwMS) under S1P or anti-CD20 with repetitive exposure to the SARS-CoV-2 virus or vaccine. The measurement of anti-SARS-CoV-2 antibody titres was performed by two independent immunoassays after initial immunisation and after booster vaccination or infection. Other laboratory and clinical parameters were included in the analysis of influencing factors. As secondary outcomes, lymphocyte and immunoglobulin levels were observed longitudinally under intravenous and subcutaneous anti-CD20 treatment. In a long-term real-world cohort of 201 pwMS, we found that despite lymphopenia upon S1P drugs, the SARS-CoV-2 immunisation response increased both in selective and non-selective S1P (100% and 88% seroconversion, respectively), whereas those under anti-CD20 therapies merely exhibited a slight long-term increase in antibody titres (52% seroconversion). The latter was independent of immunoglobulin or total lymphocyte levels, which mostly remained stable. If the individual was immunised prior to therapy initiation, their levels of SARS-CoV-2 antibodies remained high under treatment. PwMS under non-selective S1P benefit from repetitive vaccination. The risk of an insufficient vaccination response mirrored by lower SARS-CoV-2 antibodies remains in pwMS receiving anti-CD20 treatment, even after repetitive exposure to the vaccine or virus. Due to the compromised vaccination response in CD20-depleting drugs, prompt antiviral treatment might be necessary.
]]>Vaccines doi: 10.3390/vaccines12030295
Authors: Efrem Alessandro Foglia Tengiz Chaligava Tamilla Aliyeva Satenik Kharatyan Vito Tranquillo Carsten Pötzsch Cornelis van Maanen Fabrizio Rosso Santina Grazioli Emiliana Brocchi
In countries endemic for foot-and-mouth disease (FMD), routine or emergency vaccinations are strategic tools to control the infection. According to the WOAH/FAO guidelines, a prior estimation of vaccine effectiveness is recommendable to optimize control programs. This study reports the results of a small-scale immunogenicity study performed in Transcaucasian Countries. Polyvalent vaccines, including FMDV serotypes O, A (two topotypes) and Asia1 from two different manufacturers, were evaluated in Georgia, Azerbaijan and Armenia. Naïve large and small ruminants were vaccinated once and a subgroup received a second booster dose. The titers of neutralizing antibodies in sera collected sequentially up to 180 DPV were determined through the Virus Neutralization Test versus homologous strains. This study led to the estimate that both the vaccines evaluated will not induce a protective and long-lasting population immunity, even after a second vaccination, stressing that consecutive administrations of both vaccines every three months are mandatory if one aspires to achieve protective herd immunity.
]]>Vaccines doi: 10.3390/vaccines12030294
Authors: Richard Voorzaat Freek Cox Daan van Overveld Lam Le Lisanne Tettero Joost Vaneman Mark J. G. Bakkers Johannes P. M. Langedijk
Human respiratory syncytial virus (RSV) poses a significant human health threat, particularly to infants and the elderly. While efficacious vaccines based on the F protein have recently received market authorization, uncertainties remain regarding the future need for vaccine updates to counteract potential viral drift. The attachment protein G has long been ignored as a vaccine target due to perceived non-essentiality and ineffective neutralization on immortalized cells. Here, we show strong G-based neutralization in fully differentiated human airway epithelial cell (hAEC) cultures that is comparable to F-based neutralization. Next, we designed an RSV vaccine component based on the central conserved domain (CCD) of G fused to self-assembling lumazine synthase (LS) nanoparticles from the thermophile Aquifex aeolicus as a multivalent antigen presentation scaffold. These nanoparticles, characterized by high particle expression and assembly through the introduction of N-linked glycans, showed exceptional thermal and storage stability and elicited potent RSV neutralizing antibodies in a mouse model. In conclusion, our results emphasize the pivotal role of RSV G in the viral lifecycle and culminate in a promising next-generation RSV vaccine candidate characterized by excellent manufacturability and immunogenic properties. This candidate could function independently or synergistically with current F-based vaccines.
]]>Vaccines doi: 10.3390/vaccines12030293
Authors: María Dolores Manzano Javier Cereza Jesús García Luis Javier Yus Juan José Badiola Juan Emilio Echevarria Marta Monzón
Rabies, a viral disease spread by infected animal bites that causes encephalitis in humans and other mammals, is a neglected infectious disease present on all continents except Antarctica. Spain has been free of terrestrial rabies since 1978. However, due to its geographical situation, it represents a bridge for imported cases from an endemic continent such as Africa to Europe. Rabies vaccination in dogs is an essential preventive tool against this zoonosis. The aim of this study was to determine the state of the immune response against rabies virus in dogs in Spain and to demonstrate whether several factors that have been previously related to the influence of the seroprevalence of this species are involved here. The seroconversion level of this zoonotic virus was assessed in a total of 1060 animals. Indirect ELISA was used to obtain data for statistical analysis to evaluate the studied variables. Working under the concept of One Health, this study provides relevant information to be taken into consideration not only to prevent re-emergence in countries free of this disease but also for prevention and control in endemic countries.
]]>Vaccines doi: 10.3390/vaccines12030292
Authors: Yawen Zhu Rong Tang Xiaolong Li Xiaoqin Chen Xue Wang Ying Wang Ruijie Wang Fengcai Zhu Jingxin Li
This randomized, double-blind, placebo-controlled phase 1/2 trial aimed at evaluating the safety and immunogenicity of Ad5-nCoV via aerosolized or intramuscular or intramuscular–aerosolized routes in SARS-CoV-2-negative adults aged over 18 years. In the phase 1 trial, participants were sequentially enrolled into one of five regimen cohorts: Low-Dose (two doses of aerosolized Ad5-nCoV with 0.5 × 1010 viral particles [vps] per dose), Middle-Dose (two doses of aerosolized Ad5-nCoV with 1.0 × 1010 vps per dose), High-Dose (two doses of aerosolized Ad5-nCoV with 2.0 × 1010 vps per dose), Mixed (intramuscular Ad5-nCoV with 5.0 × 1010 vps [first dose] and aerosolized Ad5-nCoV with 2.0 × 1010 vps [second dose]), and Single-Dose (one dose of aerosolized Ad5-nCoV with 1.0 × 1010 vps). Eligible participants in the phase 2 trial were stratified by 18–59 years old or ≥60 years old and then were sequentially enrolled into one of six regimen cohorts: Low-Dose, Middle-Dose, High-Dose, Mixed, Single-Dose, and Intramuscular (one dose of intramuscular Ad5-nCoV with 1.0 × 1010 vps). The intervals between the two doses were 56 days. Participants were randomly allocated in 3:1 (phase 1) and 5:1 (phase 2) ratios to receive either Ad5-nCoV or the placebo in each cohort. This study is registered on ClinicalTrials.gov, NCT04840992. Most adverse reactions that occurred during the solicited period were mild and moderate. One serious adverse event (myelodysplastic syndrome) was considered potentially related to the aerosolized Ad5-nCoV. The GMTs of neutralizing antibodies in the Mixed group were the highest with 57.03 (95% CI: 23.95, 135.80) and 97.37 (95% CI: 74.30, 127.59) in phase 1 and 2 trials, respectively, 28 days after the second dose (p < 0.0001), which showed significantly higher immune responses compared to other regimens with aerosolized or intramuscular Ad5-nCoV alone.
]]>Vaccines doi: 10.3390/vaccines12030290
Authors: Dan Wu Changlei Han Suting Xiong Peipei Zhang Han Gao Junhong Li Fengming Wang Qinwen Xu Xin Dong
We aim to understand the varicella-zoster virus (VZV) antibody levels in children after vaccination and to construct VZV-IgG centile curves and reference values for children aged 1–7 years. From September to October 2023, a total of 806 children were recruited according to the time intervals of 1 month, 6 months, 1 year, 2 years, and 3 years after vaccination, as well as age groups. A generalized additive model for location, shape, and scale (GAMLSS) was applied to estimate P3, P10, P25, P50, P75, P90, and P97 centile reference values of VZV-IgG, and 95% reference intervals were calculated. A total of 785 children were included in the analysis, with an overall positivity rate of 70.3%, a median antibody concentration of 192.05 (82.89–571.14) mIU/mL, and a positivity rate of 57.7% for one dose of vaccine and 84.2% for two doses. Antibody positivity rates at 1 month, 6 months, 1 year, 2 years, and 3 years after vaccination were 65.1%, 74.4%, 80.4%, 67.7%, and 63.0%, respectively. The GAMLSS results showed that VZV-IgG had a tendency to increase and then decrease after vaccination, and the second dose of vaccination could significantly increase VZV-IgG. Two doses of varicella vaccine should be administered to children in a timely manner and included in the routine vaccination programs.
]]>Vaccines doi: 10.3390/vaccines12030291
Authors: Po-Ling Chen Tsai-Chuan Weng Chia-Chun Lai Tsai-Teng Tzeng Min-Han Lin Kai-Chieh Hu Alan Yung-Chih Hu Min-Shi Lee Wang-Chou Sung
The adaptation of egg-derived H7N9 candidate vaccine virus (CVV) in the mammalian cell line is an approach to developing a high-growth virus strain for the mass production of vaccine manufacturing. The adaptive mutations that occur in hemagglutinin (HA) are critical to the activity and potency of the vaccine virus. Previously, we identified a new mutation of A169S in the HA protein of an MDCK-adapted H7N9 vaccine virus (A/Anhui/2013, RG268); however, whether and how this mutation affects vaccine potency remain to be investigated. In this study, we serially passaged RG268 in MDCK cells and found that the HA titer and the TCID50 of the passaged virus RG268-M5 were 4-fold (HA units/50 μL) and 3.5-fold (log10 TCID50/mL) higher than those of the original CVV. By inspecting tandem MS spectra, we identified a new glycosylation site at N167 near the receptor binding site of the HA protein of RG268-M5. Flow cytometry results revealed that RG268-M5 could efficiently infect MDCK cells and initiate viral protein replication as well as that of RG268. Though the new glycosylation site is in the antigenic epitope of viral HA protein, the HI assay result indicated that the antigenicity of RG268-M5 was similar to RG268. Additionally, immunizing mice with RG268-M5 mixed aluminum hydroxide could induce potent antibody responses against the homologous and heterologous H7N9 viruses in vitro whereas the titers were comparable with those from the RG268 group. These results provide in-depth structural information regarding the effects of site-specific glycosylation on virus properties, which have implications for novel avian influenza vaccine development.
]]>Vaccines doi: 10.3390/vaccines12030289
Authors: Emily A. G. Faherty Kenneth J. Wilkins Sara Jones Anup Challa Qiuyuan Qin Lauren E. Chan Courtney Olson-Chen Jessica L. Tarleton Michael N. Liebman Federico Mariona Elaine L. Hill Rena C. Patel The N3C Consortium The N3C Consortium
COVID-19 vaccines have been shown to be effective in preventing severe illness, including among pregnant persons. The vaccines appear to be safe in pregnancy, supporting a continuously favorable overall risk/benefit profile, though supportive data for the U.S. over different periods of variant predominance are lacking. We sought to analyze the association of adverse pregnancy outcomes with COVID-19 vaccinations in the pre-Delta, Delta, and Omicron SARS-CoV-2 variants’ dominant periods (constituting 50% or more of each pregnancy) for pregnant persons in a large, nationally sampled electronic health record repository in the U.S. Our overall analysis included 311,057 pregnant persons from December 2020 to October 2023 at a time when there were approximately 3.6 million births per year. We compared rates of preterm births and stillbirths among pregnant persons who were vaccinated before or during pregnancy to persons vaccinated after pregnancy or those who were not vaccinated. We performed a multivariable Poisson regression with generalized estimated equations to address data site heterogeneity for preterm births and unadjusted exact models for stillbirths, stratified by the dominant variant period. We found lower rates of preterm birth in the majority of modeled periods (adjusted incidence rate ratio [aIRR] range: 0.42 to 0.85; p-value range: <0.001 to 0.06) and lower rates of stillbirth (IRR range: 0.53 to 1.82; p-value range: <0.001 to 0.976) in most periods among those who were vaccinated before or during pregnancy compared to those who were vaccinated after pregnancy or not vaccinated. We largely found no adverse associations between COVID-19 vaccination and preterm birth or stillbirth; these findings reinforce the safety of COVID-19 vaccination during pregnancy and bolster confidence for pregnant persons, providers, and policymakers in the importance of COVID-19 vaccination for this group despite the end of the public health emergency.
]]>Vaccines doi: 10.3390/vaccines12030288
Authors: Said A. Al-Busafi Ahmed Alwassief
Annually, more than 1.5 million preventable new hepatitis B (HBV) infections continue to occur, with an estimated global burden of 296 million individuals living with chronic hepatitis B infection. This substantial health challenge results in over 820,000 annual deaths being attributed to complications such as liver cirrhosis and hepatocellular carcinoma (HCC). The HBV vaccination remains the cornerstone of public health policy to prevent chronic hepatitis B and its related complications. It serves as a crucial element in the global effort to eliminate HBV, as established by the World Health Organization (WHO), with an ambitious 90% vaccination target by 2030. However, reports on global birth dose coverage reveal substantial variability, with an overall coverage rate of only 46%. This comprehensive review thoroughly examines global trends in HBV vaccination coverage, investigating the profound impact of vaccination on HBV prevalence and its consequences across diverse populations, including both high-risk and general demographics. Additionally, the review addresses the essential formidable challenges and facilitating factors for achieving WHO’s HBV vaccination coverage objectives and elimination strategies in the coming decade and beyond.
]]>Vaccines doi: 10.3390/vaccines12030287
Authors: Qi Wang Jian Luo Beibei Li Qian Ye Wenting Xu Feixia Gao Linting Zhou Wenyue Lu Wen-Song Tan Xiuling Li
Compared with the traditional vaccine produced in embryonated chicken eggs, cell-based manufacturing represented by the Madin–Darby canine kidney (MDCK) cell line has a larger production scale and reduces the risk of egg shortage in a pandemic. Establishing a culture system that enables high production of the influenza virus is a key issue in influenza vaccine production. Here, a serum-free suspension culture of MDCK (sMDCK) cells was obtained from adherent MDCK (aMDCK) cells by direct adaptation. Viral infection experiments showed that viral yields of influenza A/B virus in sMDCK cells were higher than in aMDCK cells. Transcriptome analysis revealed that numerous interferon-stimulated genes (ISGs) exhibited reduced expression in sMDCK cells. To further clarify the mechanism of high viral production in sMDCK cells, we demonstrated the antiviral role of RIG-I and IFIT3 in MDCK cells by knockdown and overexpression experiments. Furthermore, suppression of the JAK/STAT pathway enhances the viral accumulation in aMDCK cells instead of sMDCK cells, suggesting the reduction in the JAK/STAT pathway and ISGs promotes viral replication in sMDCK cells. Taken together, we elucidate the relationship between the host innate immune response and the high viral productive property of sMDCK cells, which helps optimize cell production processes and supports the production of cell-based influenza vaccines.
]]>Vaccines doi: 10.3390/vaccines12030286
Authors: Marcin Czech Ewa Augustynowicz Michał Byliniak Teresa Jackowska Mikołaj Konstanty Ernest Kuchar Agnieszka Mastalerz-Migas Maciej Niewada Aneta Nitsch-Osuch Iwona Paradowska-Stankiewicz Jarosław Pinkas Jakub Szulc Jacek Wysocki
This study examines the vaccine market access pathway in Poland to evaluate its efficiency and propose recommendations for its improvement. The research spans a comprehensive analysis of the vaccine assessment process, ranging from pre-registration to sustainability, encompassing critical components such as national immunization technical advisory groups (NITAGs), health technology assessments, resource evaluations, and decision making. This investigation utilizes a multi-phase approach. Initial desk research aimed to collect accumulated evidence about each step of the vaccine access pathway. This constituted the background for an expert panel discussion (n = 13) and a final online questionnaire (n = 12), evaluating the timeframes, inclusiveness, transparency, and consistency of the elements of the process. Poland is a late adopter of new vaccines. The country faces budget constraints and lacks a formalized framework for the inclusion of vaccines into the national immunization program. Notably, NITAGs play a crucial role, yet their limited resources and dependence on public health stakeholders diminish their impact. A formal and well-supported advisory body may become a foundation for decision-making processes. The health technology assessment conducted by the national agency is recognized for its timeliness and transparency, though the absence of fiscal analyses in vaccine assessments is identified as a gap that limits the understanding of the value of vaccinations. Resources are key drivers of decision making, and recent changes in legislation offer increased flexibility in financing vaccines. Challenges in the procurement process include a limited consideration of non-acquisition costs and an increased absence of a documented general strategy for immunization program development in Poland, pointing to a need for strategic planning. In conclusion, this study recommends the establishment of a robust NITAG with enhanced resources, incorporating fiscal analyses, transparent resource allocation, and strategic planning for immunization program development. Addressing these recommendations is crucial for optimizing Poland’s vaccine market access pathway, ensuring timely and efficient population-wide vaccine access.
]]>Vaccines doi: 10.3390/vaccines12030285
Authors: Kamal Fahmy Quamrul Hasan Md Sharifuzzaman Yvan Hutin
Yearly national immunization coverage reporting does not measure performance at the subnational level throughout the year and conceals inequalities within countries. We analyzed subnational immunization coverage from seven high-priority countries in our region. We analyzed subnational, monthly immunization data from seven high-priority countries. Five were Gavi eligible (i.e., Afghanistan, Pakistan, Somalia, Syria, and Yemen); these are countries that according to their low income are eligible for support from the Global Alliance on Vaccine and Immunization, while Iraq and Jordan were included because of a recent decrease in immunization coverage and contribution to the regional number of under and unimmunized children. DTP3 coverage, which is considered as the main indicator for the routine immunization coverage as the essential component of the immunization program performance, varied monthly in 2019–2021 before reaching pre-pandemic coverage in the last two months of 2021. Somalia and Yemen had a net gain in DTP3 coverage at the end of 2021, as improvement in 2021 exceeded the regression in 2020. In Pakistan and Iraq, DTP3 improvement in 2021 equaled the 2020 regression. In Afghanistan, Syria and Jordan, the regression in DTP3 coverage continued in 2020 and 2021. The number of districts with at least 6000 zero-dose children improved moderately in Afghanistan and substantially in Somalia throughout the follow-up period. In Pakistan, the geographical distribution differed between 2020 and 2021.Of the three countries with the highest number of zero-dose children, DTP1 coverage reached 109% in Q4 of 2020 after a sharp drop to 69% in Q2 of 2020. However, in Pakistan, the number of zero-dose children decreased to 1/10 of its burden in Q4 of 2021. In Afghanistan, the number of zero-dose children more than a doubled. Among the even countries, adaptation of immunization service to the pandemic varied, depending on the agility of the health system and the performance of the components of the expanded program on immunization. We recommended monitoring administrative monthly immunization coverage data at the subnational level to detect low-performing districts, plan catchup, identify bottlenecks towards reaching unvaccinated children and customize strategies to improve the coverage in districts with zero-dose children throughout the year and monitor progress.
]]>Vaccines doi: 10.3390/vaccines12030284
Authors: Anita Siller Lisa Seekircher Manfred Astl Lena Tschiderer Gregor A. Wachter Julia Penz Bernhard Pfeifer Andreas Huber Manfred Gaber Harald Schennach Peter Willeit
Background: To provide updated estimates on SARS-CoV-2 antibody seroprevalence and average antibody titres for Central Europe. Methods: In repeat cross-sectional investigations (1 May 2022 to 9 March 2023) involving 28,768 blood donors in the Federal State of Tyrol, Austria (participation rate: 87.0%), we measured Spike receptor-binding domain (RBD) and Nucleocapsid IgG antibodies (37,065 and 12,645 samples), and estimated monthly seroprevalences and geometric mean titres. Results: Median age of participants was 45.4 years (range 18–70); 43.2% were female. Spike RBD IgG antibody seroprevalence was 96.3% (95% CI: 95.6–96.9%) in May 2022, 97.4% (96.7–98.0%) in December 2022, and 97.9% (96.4–98.8%) in March 2023. Among seropositive participants, geometric mean titres increased from 1400 BAU/mL (95% CI: 1333–1471) in May 2022 to 1821 BAU/mL (1717–1932) in December 2022, and dropped to 1559 BAU/mL (1405–1729) by March 2023. Furthermore, titres differed markedly by vaccination status and history of infection, with being the highest in participants with booster vaccination and prior infection. In autumn 2022, Nucleocapsid IgG antibody seroprevalence ranged from 36.5% (35.0–38.1) in September to 39.2% (37.2–41.2) in December 2022. Conclusion: Seroprevalence of SARS-CoV-2 antibodies in blood donors from Tyrol, Austria, was remarkably stable from May 2022 to March 2023. In contrast, average Spike RBD IgG antibody titres peaked in December 2022.
]]>Vaccines doi: 10.3390/vaccines12030283
Authors: Xi Lu Lei Xu Lan Lin Liting Zhou Bingqian Dai Shuyue Cui Anding Zhang
Streptococcus suis is an important zoonotic pathogen that mainly causes meningitis, septicemia, and arthritis. Due to the limited cross-protection between numerous serotypes, the existing inactive vaccines in clinical use fail to offer sufficient protection. In this study, a gene deletion-attenuated strain Δcps/ssna-msly (P353L)-SC-19 was constructed by deleting cps and ssna genes from the epidemic strain SC-19 with a mutation of SLY (P353L). The safety of Δcps/ssna-msly (P353L)-SC-19 was confirmed in both in vitro and in vivo experiments. We further demonstrated that immunization with Δcps/ssna-msly (P353L)-SC-19 induced significant cellular immunity and humoral immunity in mice and protected against infections caused by type 2 strain SC-19 (100% protection) and type 9 strain S29 (50% protection), while also preventing meningitis induced by S29. This study highlights the potential of using CPS-deficient strains to achieve cross-protection against different Streptococcus suis serotypes and develop a promising universal live vaccine.
]]>Vaccines doi: 10.3390/vaccines12030282
Authors: Burcu Binici Zahra Rattray Avi Schroeder Yvonne Perrie
In this study, we consider the influence of biological sex-specific immune responses on the assessment of mRNA vaccines in pre-clinical murine studies. Recognising the established disparities in immune function attributed to genetic and hormonal differences between individuals of different biological sexes, we compared the mRNA expression and immune responses in mice of both biological sexes after intramuscular injection with mRNA incorporated within lipid nanoparticles. Regarding mRNA expression, no significant difference in protein (luciferase) expression at the injection site was observed between female and male mice following intramuscular administration; however, we found that female BALB/c mice exhibit significantly greater total IgG responses across the concentration range of mRNA lipid nanoparticles (LNPs) in comparison to their male counterparts. This study not only contributes to the scientific understanding of mRNA vaccine evaluation but also emphasizes the importance of considering biological sex in vaccine study designs during pre-clinical evaluation in murine studies.
]]>Vaccines doi: 10.3390/vaccines12030281
Authors: Chantelle L. White Maryah A. Glover Siva K. Gandhapudi Katherine A. Richards Andrea J. Sant
It is clear that new approaches are needed to promote broadly protective immunity to viral pathogens, particularly those that are prone to mutation and escape from antibody-mediated immunity. CD4+ T cells, known to target many viral proteins and highly conserved peptide epitopes, can contribute greatly to protective immunity through multiple mechanisms. Despite this potential, CD4+ T cells are often poorly recruited by current vaccine strategies. Here, we have analyzed a promising new adjuvant (R-DOTAP), as well as conventional adjuvant systems AddaVax with or without an added TLR9 agonist CpG, to promote CD4+ T cell responses to the licensed vaccine Flublok containing H1, H3, and HA-B proteins. Our studies, using a preclinical mouse model of vaccination, revealed that the addition of R-DOTAP to Flublok dramatically enhances the magnitude and functionality of CD4+ T cells specific for HA-derived CD4+ T cell epitopes, far outperforming conventional adjuvant systems based on cytokine EliSpot assays and multiparameter flow cytometry. The elicited CD4+ T cells specific for HA-derived epitopes produce IL-2, IFN-γ, IL-4/5, and granzyme B and have multifunctional potential. Hence, R-DOTAP, which has been verified safe by human studies, can offer exciting opportunities as an immune stimulant for next-generation prophylactic recombinant protein-based vaccines.
]]>Vaccines doi: 10.3390/vaccines12030280
Authors: Daed El Safadi Alexandre Mokhtari Morgane Krejbich Alisé Lagrave Ugo Hirigoyen Grégorie Lebeau Wildriss Viranaicken Pascale Krejbich-Trotot
Exosomes are small subtypes of extracellular vesicles (EVs) naturally released by different types of cells into their environment. Their physiological roles appear to be multiple, yet many aspects of their biological activities remain to be understood. These vesicles can transport and deliver a variety of cargoes and may serve as unconventional secretory vesicles. Thus, they play a crucial role as important vectors for intercellular communication and the maintenance of homeostasis. Exosome production and content can vary under several stresses or modifications in the cell microenvironment, influencing cellular responses and stimulating immunity. During infectious processes, exosomes are described as double-edged swords, displaying both beneficial and detrimental effects. Owing to their tractability, the analysis of EVs from multiple biofluids has become a booming tool for monitoring various pathologies, from infectious to cancerous origins. In this review, we present an overview of exosome features and discuss their particular and ambiguous functions in infectious contexts. We then focus on their properties as diagnostic or therapeutic tools. In this regard, we explore the capacity of exosomes to vectorize immunogenic viral antigens and their function in mounting adaptive immune responses. As exosomes provide interesting platforms for antigen presentation, we further review the available data on exosome engineering, which enables peptides of interest to be exposed at their surface. In the light of all these data, exosomes are emerging as promising avenues for vaccine strategies.
]]>Vaccines doi: 10.3390/vaccines12030279
Authors: Alex Olvera Luis Romero-Martin Bruna Oriol-Tordera Miriam Rosas-Umbert Tuixent Escribà Beatriz Mothe Christian Brander
The efficacy of anti-viral T-cell vaccines may greatly depend on their ability to generate high-magnitude responses targeting a broad range of different epitopes. Recently, we created the HIV T-cell immunogen HTI, designed to generate T-cell responses to protein fragments more frequently targeted by HIV controllers. In the present study, we aim to maximize the breadth and magnitude of the T-cell responses generated by HTI by combining different vaccine vectors expressing HTI. We evaluated the ability to induce strong and broad T-cell responses to the HTI immunogen through prime vaccination with DNA plasmid (D) or Chimpanzee Adenovirus Ox1 (ChAdOx1; C) vectors, followed by a Modified Virus Ankara (MVA; M) vaccine boost (DDD, DDDM, C, and CM). HTI-specific T-cell responses after vaccination were measured by IFN-γ-ELISpot assays in two inbred mice strains (C57BL/6 and BALB/c). CM was the schedule triggering the highest magnitude of the response in both mice strains. However, this effect was not reflected in an increase in the breadth of the response but rather in an increase in the magnitude of the response to specific immunodominant epitopes. Immunodominance profiles in the two mouse strains were different, with a clear dominance of T-cell responses to a Pol-derived peptide pool after CM vaccination in C57BL/6. Responses to CM vaccination were also maintained at higher magnitudes over time (13 weeks) compared to other vaccination regimens. Thus, while a ChAdOx1 prime combined with MVA booster vaccination generated stronger and more sustained T-cell responses compared to three DNA vaccinations, the ChAdOx1 primed responses were more narrowly targeted. In conclusion, our findings suggest that the choice of vaccine vectors and prime-boost regimens plays a crucial role in determining the strength, duration, breadth, and focus of T-cell responses, providing further guidance for selecting vaccination strategies.
]]>Vaccines doi: 10.3390/vaccines12030278
Authors: Violetta Opoka-Winiarska Izabela Morawska-Michalska Paulina Mertowska Krzysztof Gosik Olga Kądziołka Ewelina Grywalska
Pediatric inflammatory, multisystem syndrome temporally associated with SARS-CoV-2 infection (PIMS-TS), also known as a multisystem inflammatory syndrome in children (MIS-C), is diagnosed in children who develop an inadequate inflammatory response after exposure to the SARS-CoV-2 virus. The pathogenesis of the abnormal response of the immune system to a previous SARS-COV-2 infection has not been explained. Similarly, the safety and effectiveness of COVID-19 vaccinations in this group of patients have become the subject of clinical discussion. Presenting experiences from many centers aims to answer this question. We present 4 cases of patients who suffered from PIMS-TS. Three of them were safely vaccinated against COVID-19 after illness. One patient developed PIMS-TS temporarily associated with COVID-19 vaccination. We also collected and discussed data from other centers.
]]>Vaccines doi: 10.3390/vaccines12030277
Authors: Elena Savoia Evelyn Masterson David R. Olander Emma Anderson Anisa Mohamed Farah Luca Pirrotta
Despite the crucial role the COVID-19 vaccine played in curbing the pandemic, a significant portion of Black and African American individuals expressed hesitancy toward being vaccinated. This review aimed to identify the determinants of COVID-19 vaccine hesitancy among Black and African American individuals in the U.S. The literature search was conducted in December 2022 according to the PRISMA criteria focusing on empirical studies. Data extraction methods, critical appraisal, and secondary thematic analysis were conducted on both quantitative and qualitative studies. Sixteen quantitative studies identified the key factors associated with vaccine hesitancy, such as confidence in vaccine effectiveness, safety, and trust in the healthcare system. Fourteen qualitative studies revealed major themes of mistrust, fear, and information needs, including historical mistrust, concerns about the vaccine development process, and contemporary institutional mistrust. The synthesis of quantitative and qualitative findings derived from this review provides a nuanced understanding of the determinants of vaccine hesitancy in Black and African American communities in the U.S., offering a foundation for the development of evidence-based interventions. Mistrust in the healthcare system, fear, and informational gaps on vaccine safety and effectiveness were identified as significant barriers to vaccination, demanding targeted interventions.
]]>Vaccines doi: 10.3390/vaccines12030276
Authors: Jacob Cobb Jeffrey Rawson Nelson Gonzalez Mahmoud Singer Fouad Kandeel Mohamed I. Husseiny
A combination therapy of preproinsulin (PPI) and immunomodulators (TGFβ+IL10) orally delivered via genetically modified Salmonella and anti-CD3 promoted glucose balance in in NOD mice with recent onset diabetes. The Salmonella bacteria were modified to express the diabetes-associated antigen PPI controlled by a bacterial promoter in conjunction with over-expressed immunomodulating molecules. The possible mechanisms of action of this vaccine to limit autoimmune diabetes remained undefined. In mice, the vaccine prevented and reversed ongoing diabetes. The vaccine-mediated beneficial effects were associated with increased numbers of antigen-specific CD4+CD25+Foxp3+ Tregs, CD4+CD49b+LAG3+ Tr1-cells, and tolerogenic dendritic-cells (tol-DCs) in the spleens and lymphatic organs of treated mice. Despite this, the immune response to Salmonella infection was not altered. Furthermore, the vaccine effects were associated with a reduction in islet-infiltrating lymphocytes and an increase in the islet beta-cell mass. This was associated with increased serum levels of the tolerogenic cytokines (IL10, IL2, and IL13) and chemokine ligand 2 (CCL2) and decreased levels of inflammatory cytokines (IFNγ, GM-CSF, IL6, IL12, and TNFα) and chemokines (CXCL1, CXCL2, and CXCL5). Overall, the data suggest that the Salmonella-based vaccine modulates the immune response, reduces inflammation, and promotes tolerance specifically to an antigen involved in autoimmune diabetes.
]]>Vaccines doi: 10.3390/vaccines12030275
Authors: Paul Thöne Margot Egger Marija Geroldinger-Simic Harald Kindermann Lukas Kocik Nicola Karasek Barbara Fischerlehner Kurt Spiegl Georg Gruber Bernhard Aschacher Benjamin Dieplinger Martin Clodi Hans Geinitz
Background: Cancer patients are highly prone to infectious diseases. While undergoing antineoplastic treatment, the risk of severe symptoms upon infection increases, necessitating efficient protective measures, such as vaccination. For patients receiving radiotherapy, there is no specific information about humoral immunity. During the COVID-19 pandemic, serial antibody measurements were therefore offered to cancer patients, following SARS-CoV-2 vaccination while obtaining radiotherapy. Methods: Out of 74 enrolled patients, 46 met the inclusion criteria. Two cohorts were allocated, depending on an association with chemotherapy or pure radiotherapy. An additional healthy control cohort of 16 healthcare workers was enrolled. All participants followed a two-fold BNT162b2 vaccine schedule. SARS-CoV-2 binding antibodies were measured serially in a 7-day cycle for 35 days and over the long-term, using the Elecsys® Anti-SARS-CoV-2 immunoassay. Results: Cancer patients under pure radiotherapy have a comparable humoral vaccination response and long-term persistency of antibodies to healthy controls. Patients receiving additional chemotherapy show a significantly delayed immune response and decreased antibody titers. The vaccine was well tolerated in all cohorts. Conclusions: Pure radiotherapy in cancer patients does not interfere with the vaccine-induced humoral immune response or other immunogenetic aspects, whereas previous or simultaneous chemotherapy does. Findings are of particular relevance for future epidemic or pandemic scenarios.
]]>Vaccines doi: 10.3390/vaccines12030274
Authors: Ruth Xian Lynn Yap Yi Wye Lai Chang Wei Joel Jia Wei Ng Dan Xu Shuo Feng Rong Mu Bernard Yu-Hor Thong Chuanhui Xu
Coronavirus disease 2019 (COVID-19) vaccination is essential for patients with autoimmune inflammatory rheumatic diseases (AIIRD) to reduce the risk of morbidity and mortality associated with serious COVID-19 infection. With endemicity, waning of vaccine- and infection-acquired immunity, and development of SARS-CoV-2 variants, the need for additional doses of vaccines against serious illness in high-risk immunocompromised persons remains imperative. This review examines how immunomodulatory therapies affect vaccine-induced immune response in patients with AIIRD. Glucocorticoids, methotrexate, azathioprine, calcineurin inhibitors, mycophenolate mofetil, tumor necrosis factor inhibitors, and abatacept have been shown to variably attenuate both humoral and cellular immune responses to vaccination. Janus kinase inhibitors reduce humoral immune response. In contrast, sulfasalazine, leflunomide, belimumab, interleukin (IL)-17, IL-12/23, IL-6, and IL-1 inhibitors appear favorable, with mild or no impact on vaccine response. Although rituximab is known to profoundly diminish humoral immune response, cellular immunity is relatively preserved. Administering a third and subsequent vaccine dose or temporally coordinating the dosing of immunomodulatory drugs may improve vaccine effectiveness. Further research is needed to personalise vaccination strategies for AIIRD patients, considering their specific immunomodulatory treatments.
]]>Vaccines doi: 10.3390/vaccines12030273
Authors: Lerato P. Kgosana Mapaseka L. Seheri Cliff A. Magwira
Bacterial lipopolysaccharides (LPSs) have been shown to promote enteric viral infections. This study tested the hypothesis that elevated levels of bacterial LPS improve oral rotavirus vaccine replication in South African infants. Stool samples were collected from infants a week after rotavirus vaccination to identify vaccine virus shedders (n = 43) and non-shedders (n = 35). Quantitative real-time PCR was used to assay for selected LPS-rich bacteria, including Serratia marcescens, Pseudomonas aeruguinosa and Klebsiella pneumonia, and to measure the gene expression of bacterial LPS, host Toll-like Receptor 4 (TLR4) and Interleukin-8 (IL-8). The abundance of selected LPS-rich bacteria was significantly higher in vaccine shedders (median log 4.89 CFU/g, IQR 2.84) compared to non-shedders (median log 3.13 CFU/g, IQR 2.74), p = 0.006. The TLR4 and IL-8 gene expressions were increased four- and two-fold, respectively, in vaccine shedders versus non-shedders, but no difference was observed in the bacterial LPS expression, p = 0.09. A regression analysis indicated a significant association between the abundance of selected LPS-rich bacteria and vaccine virus shedding (Odds ratio 1.5, 95% CI = 1.10–1.89), p = 0.002. The findings suggest that harbouring higher counts of LPS-rich bacteria can increase the oral rotavirus vaccine take in infants.
]]>Vaccines doi: 10.3390/vaccines12030272
Authors: Jingyi Fan Istvan Toth Rachel J. Stephenson
Group A Streptococcus (GAS), or Streptococcus pyogenes, is a gram-positive bacterium that extensively colonises within the human host. GAS is responsible for causing a range of human infections, such as pharyngitis, impetigo, scarlet fever, septicemia, and necrotising fasciitis. GAS pathogens have the potential to elicit fatal autoimmune sequelae diseases (including rheumatic fever and rheumatic heart diseases) due to recurrent GAS infections, leading to high morbidity and mortality of young children and the elderly worldwide. Antibiotic drugs are the primary method of controlling and treating the early stages of GAS infection; however, the recent identification of clinical GAS isolates with reduced sensitivity to penicillin-adjunctive antibiotics and increasing macrolide resistance is an increasing threat. Vaccination is credited as the most successful medical intervention against infectious diseases since it was discovered by Edward Jenner in 1796. Immunisation with an inactive/live-attenuated whole pathogen or selective pathogen-derived antigens induces a potent adaptive immunity and protection against infectious diseases. Although no GAS vaccines have been approved for the market following more than 100 years of GAS vaccine development, the understanding of GAS pathogenesis and transmission has significantly increased, providing detailed insight into the primary pathogenic proteins, and enhancing GAS vaccine design. This review highlights recent advances in GAS vaccine development, providing detailed data from preclinical and clinical studies across the globe for potential GAS vaccine candidates. Furthermore, the challenges and future perspectives on the development of GAS vaccines are also described.
]]>Vaccines doi: 10.3390/vaccines12030271
Authors: Diana Souza de Oliveira Maykelin Fuentes Zaldívar Ana Alice Maia Gonçalves Lucilene Aparecida Resende Reysla Maria da Silveira Mariano Diogo Fonseca Soares Pereira Ingrid dos Santos Soares Conrado Mariana Amália Figueiredo Costa Daniel Ferreira Lair Diego Fernandes Vilas-Boas Eiji Nakasone Nakasone Ingrid de Sousa Ameno Wanessa Moreira Goes Denise Silveira-Lemos Alexsandro Sobreira Galdino Ronaldo Alves Pinto Nagem Walderez Ornelas Dutra Rodolfo Cordeiro Giunchetti
The development of prophylactic vaccines is important in preventing and controlling diseases such as visceral leishmaniasis (VL), in addition to being an economic measure for public health. Despite the efforts to develop a vaccine against human VL caused by Leishmania infantum, none is available, and the focus has shifted to developing vaccines against canine visceral leishmaniasis (CVL). Currently, commercially available vaccines are targeted at CVL but are not effective. Different strategies have been applied in developing and improving vaccines, such as using chimeric proteins to expand vaccine coverage. The search for patents can be a way of tracking vaccines that have the potential to be marketed. In this context, the present work presents a summary of immunological aspects relevant to VL vaccine development with a focus on the composition of chimeric protein vaccines for CVL deposited in patent banks as an important approach for biotechnological development. The resulting data could facilitate the screening and selection of antigens to compose vaccine candidates with high performance against VL.
]]>Vaccines doi: 10.3390/vaccines12030270
Authors: Vassiliki C. Pitiriga Myrto Papamentzelopoulou Kanella E. Konstantinakou Irene V. Vasileiou Alexandros D. Konstantinidis Natalia I. Spyrou Athanasios Tsakris
Introduction: Exploring T cell response duration is pivotal for understanding immune protection evolution in natural SARS-CoV-2 infections. The objective of the present study was to analyze the T cell immune response over time in individuals who were both vaccinated and COVID-19-naive and had undetectable levels of SARS-CoV-2 IgG antibodies at the time of testing. Methods: We performed a retrospective descriptive analysis using data extracted from the electronic medical records of consecutive adult individuals who underwent COVID-19 immunity screening at a private healthcare center from September 2021 to September 2022. The study participants were divided into three groups according to the post-vaccination time period, as follows: group A (up to 3 months), group B (3–6 months), and group C (>6 months). T cell response was evaluated using the IGRA methodology T-SPOT®.COVID. Results: Of the total number of subjects (n = 165), 60/165 (36.4%) had been vaccinated in the last 3 months (group A), 57/165 (34.5%) between 3 and 6 months (group B), and 48/165 (29.1%) at least 6 months prior to the examination day (group C). T cell positivity was reported in 33/60 (55.0%) of group A, 45/57 (78.9%) of group B, and 36/48 (75%) of group C (p < 0.007). No statistically significant differences were revealed in the spot-forming cell (SFC) count among groups, with mean SFC counts of 75.96 for group A, 89.92 for group B, and 83.58 for group C (Kruskal–Wallis test, p = 0.278). Conclusions: Our findings suggest that cellular immunity following SARS-CoV-2 vaccination may endure for at least six months, even in the presence of declining or absent IgG antibody levels.
]]>Vaccines doi: 10.3390/vaccines12030269
Authors: Josephine Etowa Sheryl Beauchamp Manal Fseifes Glory Osandatuwa Paul Brenneman Kudirat Salam-Alada Rasheedaht Sulaiman Emmanuella Okolie Ihechi Dinneh Samora Julmisse Victoria Cole
Although the COVID-19 pandemic has caused the need for the largest mass vaccination campaign ever undertaken to date, African, Caribbean, and Black (ACB) populations have shown both a disproportionately high degree of negative impacts from the pandemic and the lowest willingness to become vaccinated. This scoping review aims to investigate low vaccine uptake in ACB populations relative to public health in high-income countries. A search was conducted in MEDLINE(R) ALL (OvidSP), Embase (OvidSP), CINAHL (EBSCOHost), APA PsycInfo (OvidSP), the Cochrane Central Register of Controlled Trials (OvidSP), the Cochrane Database of Systematic Reviews (OvidSP), the Allied and Complimentary Medicine Database (Ovid SP), and the Web of Science following the Joanna Briggs Institute (JBI) framework for scoping reviews, supplemented by PRISMA-ScR. Theoretical underpinnings of the intersectionality approach were also used to help interpret the complexities of health inequities in the ACB population. The eligibility criteria were based on the population, concept, context (PCC) framework, and publications from 2020–19 July 2022 which discussed vaccine uptake amongst ACB people in high-income countries were included. Analysis was carried out through thematic mapping and produced four main themes: (1) racism and inequities, (2) sentiments and behaviors, (3) knowledge and communication, and (4) engagement and influence. This study has contributed to the identification and definition of the issue of low vaccine uptake in ACB populations and has illustrated the complexity of the problems, as vaccine access is hampered by knowledge, psychological, socioeconomic, and organizational barriers at the individual, organizational, and systemic levels, leading to structural inequities that have manifested as low vaccine uptake.
]]>Vaccines doi: 10.3390/vaccines12030268
Authors: Kai Wei Lee Sook Fan Yap Hooi Tin Ong Sien Leong Liew Myo Oo Kye Mon Min Swe
The elderly are considered a high-risk group for severe outcomes and death from COVID-19 infection. Given the emergence of new COVID variants and the immunity provided by vaccines waning over time, booster doses of the vaccine have been advocated for those at risk to stay protected. This study aimed to determine the factors associated with hesitancy toward the second booster of the COVID-19 vaccine among the elderly residing in residential care homes. A cross-sectional study was conducted in 24 residential care homes in the Klang Valley using a face-to-face interview questionnaire. The study population included individuals aged 60 and above who had been fully vaccinated against COVID-19 up to the first booster dose. Second-booster hesitancy was assessed using the Oxford Vaccine Hesitancy Scale with seven items, the aggregate score of which ranges from seven to thirty-five; the higher the score, the greater the level of hesitancy. Multivariate linear regression was employed to determine factors associated with second-booster hesitancy, and a p-value < 0.05 was considered statistically significant. Data from 401 elderly individuals were included for analysis. The mean score of the Oxford Vaccine Hesitancy Scale was 21.6 ± 7.2. Predictors of second booster hesitancy were identified. Age, Indian ethnicity, being a recipient of the Sinovac vaccine as the first COVID-19 booster, experiencing the death of close friends or immediate family members following COVID-19 vaccination, and negative messages (indicating that taking a booster dose is harmful) from caregivers, friends, or family members were found to be associated with an increased second-booster-hesitancy score. Conversely, positive messages (indicating that taking a booster is helpful) from the government and caregivers, friends, or family members were identified as predictors associated with a reduction in the second-booster-hesitancy score. While vaccines effectively combat severe COVID-19, the majority of the elderly hesitate before taking the second booster. Their hesitancy, rooted in the perception of a low self risk and reliance on protection from the initial doses, emphasizes the need for intervention by relevant bodies. Taking into consideration the risk, albeit relatively low, of potentially serious side effects following COVID-19 vaccinations, it is imperative that transparent, appropriate, and positive messaging regarding booster vaccines, particularly in the context of the elderly from residential care homes, be available. Encouraging this high-risk group to embrace the second booster aligns with the goal of maximizing protection within the vulnerable elderly population.
]]>Vaccines doi: 10.3390/vaccines12030266
Authors: Mahima T. Rasquinha Kiruthiga Mone Meghna Sur Ninaad Lasrado Chandirasegaran Massilamany Stephen D. Kachman David Steffen Jay Reddy
Group B coxsackieviruses (CVBs) cause a wide range of diseases in humans, but no vaccines are currently available to prevent these infections. Previously, we had demonstrated that a live attenuated CVB3 vaccine virus, Mutant 10 (Mt10), offers protection against multiple CVB serotypes as evaluated in various inbred mouse strains; however, the applicability of these findings to the outbred human population remains uncertain. To address this issue, we used Diversity Outbred (DO) mice, whose genome is derived from eight inbred mouse strains that may capture the level of genetic diversity of the outbred human population. To determine the efficacy of the Mt10 vaccine, we established the CVB3 infection model in the DO mice. We noted that CVB3 infection resulted mainly in pancreatitis, although viral RNA was detected in both the pancreas and heart. Histologically, the pancreatic lesions comprised of necrosis, post-necrotic atrophy, and lymphocyte infiltration. In evaluating the efficacy of the Mt10 vaccine, both male and female DO mice were completely protected in challenge studies with CVB3, and viral RNA was not detected in the heart or pancreas. Likewise, vaccine recipients of both sexes showed significant levels of virus-neutralizing antibodies. Furthermore, by using the CVB3 viral protein 1, virus-reactive antibodies were found to be diverse in the order of IgG2c, followed by IgG2a, IgG2b/IgG3, and IgG1. Together, the data suggest that the Mt10 vaccine virus can offer protection against CVB infections that may have translational significance.
]]>Vaccines doi: 10.3390/vaccines12030267
Authors: Ivars Petrovskis Dace Skrastina Juris Jansons Andris Dislers Janis Bogans Karina Spunde Anastasija Neprjakhina Jelena Zakova Anna Zajakina Irina Sominskaya
Virus-like particles (VLPs) offer an attractive possibility for the development of vaccines. Recombinant core antigen (HBc) of Hepatitis B virus (HBV) was expressed in different systems, and the E. coli expression system was shown to be effective for the production of HBc VLPs. Here, we used HBc of the HBV genotype G (HBc/G) as a technologically promising VLP carrier for the presentation of spike RBM and nucleocapsid protein-derived peptides of the SARS-CoV-2 Delta variant for subsequent immunological evaluations of obtained fusion proteins. The major immunodominant region (MIR) of the HBc/G protein was modified through the insertion of a receptor binding motif (RBM) from the S protein or B-cell epitope-containing peptide from the N protein. The C-terminus of the two truncated HBc/G proteins was used for the insertion of a group of five cytotoxic T lymphocyte (CTL) epitopes from the N protein. After expression in E. coli, the MIR-derived proteins were found to be insoluble and were recovered through step-wise solubilization with urea, followed by refolding. Despite the lack of correct VLPs, the chimeric proteins induced high levels of antibodies in BALB/c mice. These antibodies specifically recognized either eukaryotically expressed hRBD or bacterially expressed N protein (2–220) of SARS-CoV-2. CTL-epitope-containing proteins were purified as VLPs. The production of cytokines was analyzed through flow cytometry after stimulation of T-cells with target CTL peptides. Only a protein with a deleted polyarginine (PA) domain was able to induce the specific activation of T-cells. At the same time, the T-cell response against the carrier HBc/G protein was detected for both proteins. The neutralization of SARS-CoV-2 pseudotyped murine retrovirus with anti-HBc/G-RBM sera was found to be low.
]]>Vaccines doi: 10.3390/vaccines12030265
Authors: Hernan Inojosa Dirk Schriefer Yassin Atta Anja Dillenseger Undine Proschmann Katharina Schleußner Christina Woopen Tjalf Ziemssen Katja Akgün
The SARS-CoV-2 pandemic profoundly impacted people with multiple sclerosis (pwMS). Disease-related aspects and demographic factors may influence vaccination rates, infection susceptibility, and severity. Despite prior research, comprehensive real-world data obtained throughout the pandemic remain limited. We investigated SARS-CoV-2 vaccination and infection patterns in a large monocentric real-world cohort. We collected prospective data from medical visits at the MS Center Dresden, Germany, from the pandemic’s beginning until 31 May 2022. Logistic regression and rank correlation analyses were used to explore associations between SARS-CoV-2 outcomes and patient characteristics. Of 2115 pwMS assessed (mean age 46.5, SD ± 12.9; median expanded disability status scale 2.5), 77.9% were under disease-modifying treatment (DMT), primarily B-cell depletion (25.4%). A total of 35.5% reported SARS-CoV-2 infections, and 77.4% were fully vaccinated. PwMS with increased disability, older age, and comorbidities were associated with higher vaccination rates, possibly due to the awareness of these populations regarding complications of SARS-CoV-2 infections. Infections were more common in younger females, people with a lower degree of disability, those with relapsing MS, and those who were not vaccinated. PwMS on B-cell depletion reported more infections than untreated pwMS and those receiving other types of disease-modifying therapy, despite higher vaccination rates. Most infections were mild, with no severity differences according to demographic or disease-related factors, except for gender. Notably, all fatal cases occurred in unvaccinated pwMS. Our studies suggest that demographic and disease-related factors, especially age and the use of B-cell depletion, significantly influenced SARS-CoV-2 vaccination and infection rates in our cohort. These factors may be considered in future preventive campaigns in further pandemics.
]]>Vaccines doi: 10.3390/vaccines12030264
Authors: Domenico Tripodi Roberto Dominici Davide Sacco Gennaro Santorelli Rodolfo Rivera Sandro Acquaviva Marino Marchisio Paolo Brambilla Graziana Battini Valerio Leoni
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a high rate of mortality in kidney transplant recipients (KTRs). Current vaccine strategies for KTRs seem to be unable to provide effective protection against coronavirus disease 2019 (COVID-19), and the occurrence of severe disease in some vaccinated KTRs suggested a lack of immunity. We initially analyzed the antibody response in a group of 32 kidney transplant recipients (KTRs) followed at the nephrology and dialysis unit of the Hospital Pio XI of Desio, ASST-Brianza, Italy. Thus, we studied the differences in antibody levels between subjects who contracted SARS-CoV-2 after the booster (8 individuals) and those who did not contract it (24 individuals). Furthermore, we verified if the antibody response was in any way associated with creatinine and eGFR levels. We observed a significant increase in the antibody response pre-booster compared to post-booster using both a Roche assay and DIAPRO assay. In the latter, through immunotyping, we highlight that the major contribution to this increase is specifically due to IgG S1 IgM S2. We observed a significant increase in IgA S1 and IgA NCP (p = 0.045, 0.02) in the subjects who contracted SARS-CoV-2. We did not find significant associations for the p-value corrected for false discovery rate (FDR) between the antibody response to all assays and creatinine levels. This observation allows us to confirm that patients require additional vaccine boosters due to their immunocompromised status and therapy in order to protect them from infections related to viral variants. This is in line with the data reported in the literature, and it could be worthwhile to deeply explore these phenomena to better understand the role of IgA S1 and IgA NCP antibodies in SARS-CoV-2 infection.
]]>Vaccines doi: 10.3390/vaccines12030263
Authors: Wenjian Liu Meng Liu Shuaiwen Wang Zhihui Tang Jiwen Liu Suquan Song Liping Yan
Hepatitis-hydropericardium syndrome (HHS), caused by fowl adenovirus serotype 4 (FAdV-4), has been widely spread across China, resulting in great financial losses in the poultry industry. Therefore, efficient vaccines against this disease urgently need to be developed. In our study, the fiber-2 and penton base proteins derived from the FAdV-4 JS strain were expressed in a prokaryotic system (E. coli) in a soluble form. Then, the efficacy of the two recombinant proteins formulated with cheap and widely used adjuvants (Marcol™ 52 white oil) were respectively tested, and the minimum immune doses and safety of the above proteins were also determined. It was indicated that the fiber-2 (20 µg/bird, 200 µg/bird) and penton base (200 µg/bird) could provide complete protection against the highly pathogenic FAdV-4 and suppress its replication and shedding. Unfortunately, only the fiber-2 protein could induce complete protection (10/10) at a low dose (10 µg/bird). In addition, we confirmed that the fiber-2 subunit vaccine formulated with oil adjuvants was safe for vaccinated chickens. Conclusively, all of our results suggest that we successfully prepared an efficient and cheap fiber-2 subunit vaccine with few side effects.
]]>Vaccines doi: 10.3390/vaccines12030262
Authors: Walid Al-Qerem Anan Jarab Judith Eberhardt Fawaz Alasmari Alaa Hammad Sarah Abu Hour
There is a critical need to understand vaccine decision-making in high-risk groups. This study explored flu vaccine acceptance among Jordanian parents of diabetic children. Employing a cross-sectional approach, 405 parents from multiple healthcare centers across Jordan were recruited through stratified sampling, ensuring a broad representation of socioeconomic backgrounds. A structured questionnaire, distributed both in-person and online, evaluated their knowledge, attitudes, and acceptance of the flu vaccine for their diabetic children. The results indicated that only 6.4% of the study sample reported vaccinating their children against the flu annually, and only 23% are planning to vaccinate their children this year. A multinomial logistic regression analysis revealed notable variability in responses. Specifically, parents with a positive attitude towards the flu vaccine and those with older children had less odds to reject the vaccine (OR = 0.589, 95% CI (0.518–0.670), p < 0.001 and OR = 0.846, 95% CI (0.736–0.974), p = 0.02, respectively). Conversely, prevalent misconceptions regarding vaccine safety and efficacy emerged as significant barriers to acceptance. Our findings advocate for targeted educational programs that directly address and debunk these specific misconceptions. Additionally, strengthened healthcare communication to provide clear, consistent information about the flu vaccine’s safety and benefits is vital to help enhance vaccine uptake among this vulnerable population, emphasizing the need to address specific concerns and misinformation directly.
]]>Vaccines doi: 10.3390/vaccines12030261
Authors: Qiao Wen Tee Ramin Odisho Elisha Purcell Rachael Purcell Jim Buttery Claudia A. Nold-Petry Marcel F. Nold Atul Malhotra
Introduction: The World Health Organization (WHO) recommends vaccination against hepatitis B as soon as possible following birth for all infants, regardless of prematurity. Hepatitis B vaccination at birth is clearly justified, represents a crucial step in the global control of perinatally acquired hepatitis B and there are no safety concerns in infants born at term. However, there is limited information on the safety of the hepatitis B vaccine in preterm infants, whose immune responses and morbidity risk differ from those in infants born at term. Objectives: The objectives of this paper are to systematically review the literature regarding the safety and risk of adverse events following immunisation (AEFIs) associated with the administration of the hepatitis B vaccine (monovalent or as part of a combination vaccine) to preterm infants. Methods: We performed a search for relevant papers published between 1 January 2002 and 30 March 2023 in the Ovid MEDLINE, Ovid Embase, Cochrane Central Register of Controlled Trials and CINAHL Plus databases. Two authors independently reviewed and analysed each article to include in the systematic review. Narrative synthesis is presented. Results: Twenty-one relevant papers were identified and included in this systematic review. The vast majority of data pertained to multi-antigen (combination) vaccine preparations and vaccination episodes from 6 weeks of age onwards. We found no publications investigating the timing of the birth dose of the hepatitis B vaccine, and AEFI reporting was exclusively short-term (hours to days following administration). There was substantial variability in the reported rate of AEFIs between studies, ranging from 0% to 96%. Regardless of frequency, AEFIs were mostly minor and included injection site reactions, temperature instability and self-limiting cardiorespiratory events. Six studies reported serious adverse events (SAEs) such as the requirement for escalation of respiratory support. However, these occurred predominantly in high-risk infant populations and were rare (~1%). Using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach, the certainty of evidence was assessed as very low. Conclusions: Despite substantial variability between the relatively small number of published studies in terms of cohort selection, definitions, vaccine preparations and reporting, hepatitis B-containing vaccines (mostly as combination vaccines) appear to be relatively well tolerated in preterm infants from 6 weeks of age. Research focusing on the safety of hepatitis B vaccine in preterm infants specifically within 7 days of birth is lacking, particularly regarding long-term morbidity risk. Further research in this area is required.
]]>Vaccines doi: 10.3390/vaccines12030260
Authors: Casey Hensley Sandro Roier Peng Zhou Sofia Schnur Charlotte Nyblade Viviana Parreno Annie Frazier Maggie Frazier Kelsey Kiley Samantha O’Brien Yu Liang Bryan T. Mayer Ruizhe Wu Celia Mahoney Monica M. McNeal Benjamin Petsch Susanne Rauch Lijuan Yuan
Human rotavirus (HRV) is still a leading cause of severe dehydrating gastroenteritis globally, particularly in infants and children. Previously, we demonstrated the immunogenicity of mRNA-based HRV vaccine candidates expressing the viral spike protein VP8* in rodent models. In the present study, we assessed the immunogenicity and protective efficacy of two mRNA-based HRV trivalent vaccine candidates, encoding VP8* of the genotypes P[8], P[6], or P[4], in the gnotobiotic (Gn) pig model of Wa (G1P[8]) HRV infection and diarrhea. Vaccines either encoded VP8* alone fused to the universal T-cell epitope P2 (P2-VP8*) or expressed P2-VP8* as a fusion protein with lumazine synthase (LS-P2-VP8*) to allow the formation and secretion of protein particles that present VP8* on their surface. Gn pigs were randomly assigned into groups and immunized three times with either P2-VP8* (30 µg) or LS-P2-VP8* (30 µg or 12 µg). A trivalent alum-adjuvanted P2-VP8* protein vaccine or an LNP-formulated irrelevant mRNA vaccine served as the positive and negative control, respectively. Upon challenge with virulent Wa HRV, a significantly shortened duration and decreased severity of diarrhea and significant protection from virus shedding was induced by both mRNA vaccine candidates compared to the negative control. Both LS-P2-VP8* doses induced significantly higher VP8*-specific IgG antibody titers in the serum after immunizations than the negative as well as the protein control. The P[8] VP8*-specific IgG antibody-secreting cells in the ileum, spleen, and blood seven days post-challenge, as well as VP8*-specific IFN-γ-producing T-cell numbers increased in all three mRNA-vaccinated pig groups compared to the negative control. Overall, there was a clear tendency towards improved responses in LS-P2-VP8* compared to the P2-VP8*mRNA vaccine. The demonstrated strong humoral immune responses, priming for effector T cells, and the significant reduction of viral shedding and duration of diarrhea in Gn pigs provide a promising proof of concept and may provide guidance for the further development of mRNA-based rotavirus vaccines.
]]>Vaccines doi: 10.3390/vaccines12030259
Authors: Ryo Okuyama
Various vaccine platforms, including emerging platforms, have been applied in the development of COVID-19 vaccines. Biotechnology startups often lead the development of new medical technologies, whereas major pharmaceutical companies and public institutions have long contributed to vaccine development. In this study, vaccine platforms and developers involved in COVID-19 vaccine development were analyzed, elucidating the trends of vaccine platforms used, the country distribution of the developers, and differences in the profiles of developers by vaccine platform technologies and country. The analysis revealed that conventional, established, and emerging vaccine platforms have been widely used and that older platforms are more advanced in clinical development. It also demonstrated the emergence of China, in addition to the U.S., while many pharmerging countries have been engaged in development. Startups have significantly contributed to the development of viral vector and RNA-based vaccines, suggesting their important role in the application of novel technologies. The major developers differ by country and region. Alliances, including international collaborations, have progressed in late clinical development. Based on these results, future perspectives of pandemic vaccine development and implications for policy and corporate strategies are discussed.
]]>Vaccines doi: 10.3390/vaccines12030257
Authors: Jorian Fiers Dominiek Maes Ann-Brigitte Cay Frank Vandenbussche Laurent Mostin Anna Parys Marylène Tignon
Vaccination against the Porcine Reproductive and Respiratory Syndrome virus (PRRSV) is widely practiced in both sows and piglets. However, it has been shown that multivaccinated sows sometimes lack a detectable antibody response, testing seronegative in ELISA (non-responders). Moreover, PRRSV-vaccinated piglets can remain seronegative as well, which is mainly attributed to the interference of maternally derived antibodies (MDAs). The current study investigated the impact of the sow’s immune status on the PRRSV vaccine effectiveness in the progeny. The experimental trial included forty-eight piglets (n = 48) originating from a commercial Belgian breeding herd, with twenty-four piglets born from PRRSV vaccinated responder sows (E+ piglets) and twenty-four piglets born from PRRSV vaccinated non-responder sows (E− piglets). Eight piglets in each group were either non-vaccinated (NoVac piglets; n = 8), intramuscularly vaccinated (IM piglets; n = 8), or intradermally vaccinated (ID piglets; n = 8), with the same PRRSV-1 vaccine as used in the sow population. Vaccination was performed at weaning at three weeks of age, and all study piglets were challenged with a high dose of the PRRSV-1 07V063 strain at 6 weeks of age. A clear interference of MDAs was observed in the E+ piglets: 66.7% of the vaccinated E+ piglets lacked an antibody response at 3 weeks post-vaccination (non-responders). Consequently, post-challenge, only the responding E+ piglets had a significantly reduced serum viremia compared to the E+ NoVac piglets. The observed viremia in the non-responding E+ piglets was similar to the viremia of the E+ NoVac piglets. In the vaccinated E− piglets, a lack of antibody response at 3 weeks post-vaccination was observed in 18.8% of the piglets. Interestingly, despite the lack of a vaccine antibody response, the non-responding E− piglets had a significantly reduced serum viremia compared to the NoVac E− piglets. In contrast, the viremia of the responding E− piglets was only numerically reduced compared to the NoVac E− piglets. Finally, some clear differences were observed in both the kinetics of infection and the immune responses post-challenge between the E+ and E− piglets. The results of this study confirm the consequences of the MDA interference on the induced partial protection of PRRSV vaccination in experimentally challenged piglets. More research is warranted to understand the immunological mechanisms behind MDA interference in PRRSV vaccination and to explain the observed differences between E+ and E− piglets.
]]>Vaccines doi: 10.3390/vaccines12030258
Authors: Fabrizio Bert Giuseppina Lo Moro Francesco Calabrese Valentino Barattero Alberto Peano Giacomo Scaioli Roberta Siliquini
In recent decades, the rise of zoonotic diseases has emerged as a significant human health concern, highlighting the interconnectedness of human and animal health within the framework of the “One Health” (OH) concept. This study, conducted in Italy in 2023, sought to gauge the general population’s awareness of OH and zoonotic diseases while identifying influencing factors. Additionally, it aimed to assess awareness of an Mpox virus vaccine, particularly pertinent due to the 2022 outbreak across Europe. The online cross-sectional study encompassed 1058 participants, revealing that 54.26% were unfamiliar with OH and zoonoses. Median knowledge scores were 12 points (IQR = 9–15) for zoonoses and 8 points (IQR = 6–11) for OH. Notably, factors such as age, economic situation, healthcare employment, educational level, and health literacy significantly influenced knowledge scores. Merely 26.8% of participants were aware of the existence of an Mpox vaccine, with healthcare workers, individuals engaged in animal-related work, and non-heterosexual men demonstrating higher awareness. The findings underscored a limited public understanding of zoonotic diseases and One Health, with variations observed across specific demographic groups. Given the potential impact on public health, urgent educational initiatives are warranted. Moreover, the study highlighted a low awareness of the Mpox vaccine, emphasizing the necessity for targeted awareness campaigns directed at both professionals and the general public.
]]>Vaccines doi: 10.3390/vaccines12030256
Authors: Davide Graci Nicolò Piazza Salvatore Ardagna Alessandra Casuccio Anton Drobov Federica Geraci Angelo Immordino Alessandra Pirrello Vincenzo Restivo Riccardo Rumbo Rosalba Stefano Roberta Virone Elena Zarcone Palmira Immordino
Human papillomavirus (HPV) is the most prevalent sexually transmitted virus globally and a primary cause of cervical cancer, which ranks fourth among tumors in both incidence and mortality. Despite the availability of effective vaccines worldwide, HPV vaccination rates vary, especially among migrant and refugee populations. Indeed, migrant status may act as a determinant against accessing vaccinations, among many other factors. The objective of this paper is to evaluate barriers to and facilitators for accessing HPV vaccination in migrant and refugee populations. A systematic review of the existing peer-reviewed academic literature was conducted according to the PRISMA 2020 guidelines in which we examined thirty-four studies to evaluate HPV vaccination rates in these populations and identify factors acting as barriers or facilitators. Key determinants include socio-economic status and health literacy. Communication barriers, including language and cultural factors, also impact access to information and trust in the health workforce. Understanding and considering these factors is crucial for developing proper and inclusive vaccination strategies to ensure that no population is overlooked.
]]>Vaccines doi: 10.3390/vaccines12030255
Authors: Joanna Kulikowska Katarzyna Kapica-Topczewska Monika Gudowska-Sawczuk Agnieszka Kulczyńska-Przybik Marcin Bazylewicz Anna Mirończuk Agata Czarnowska Waldemar Brola Barbara Mroczko Jan Kochanowicz Alina Kułakowska
The coronavirus 2019 disease (COVID-19) course and serological statuses of patients with relapsing–remitting multiple sclerosis (RRMS), treated with disease-modifying therapies (DMTs) are generally parallel that of the general population. Over the pandemic’s course, however, a notable increase in the number of RRMS patients who received vaccination against severe acute respiratory coronavirus 2 (SARS-CoV-2) and those who had COVID-19 (symptomatic and asymptomatic) was reported. This virus and/or vaccination likely influenced DMT-treated RRMS patients’ serological statuses regarding the presence of SARS-CoV-2 antibodies and their quantitative expression. This investigation assesses the presence and levels of the antibody directed against the S1 protein receptor binding domain (SRBD) and against the N protein of SARS-CoV-2 in 38 DMT-treated RRMS patients. The findings indicate that people vaccinated against SARS-CoV-2 exhibited significantly higher levels of IgG antibodies against S1-RBD at both assessment points. Patients with a prior history of COVID-19 demonstrated statistically significant increases in anti-N antibodies at visit 1, whereas such statistical significance was not observed at visit 2. DMT-treated RRMS patients generated neutralizing antibodies following vaccination and/or COVID-19 infection. Nevertheless, it is noteworthy that antibody levels more accurately reflect the serological status and exhibit a stronger correlation with vaccination than just the presence of antibodies.
]]>Vaccines doi: 10.3390/vaccines12030254
Authors: Luca Cegolon Francesca Larese Filon
Background: The risk of COVID-19 increases in any occupation entailing intense social interactions. This study aimed to investigate the impact of COVID-19 among civil servants of Trieste city council (northeastern Italy) over the entire pandemic. Methods: The crude incidence rate of COVID-19 was estimated from 1 March 2020 to 31 January 2023 by explanatory factors, expressing the estimate as COVID-19 events x 10,000 person-days (P-d) at risk. A multivariable Cox proportional hazard regression model was fitted to examine the risk of primary COVID-19 infection and reinfections, reporting adjusted hazard ratios (aHR) with 95% confidence interval (95% CI). Results: The cohort of Trieste city council was mainly composed of administrative clerks (48.5%), nursery teachers (33%), technicians (9.9%) and local police officers (8.5%). Between 1 March 2020 and 31 January 2023, 1444 (62.4%) employees tested positive for SARS-CoV-2 at least once and 18.1% (=262/1444) at least twice. By the end of this study, 55% (N = 1272) of employees had received at least three doses of COVID-19 vaccine, whereas 19.7% (N = 457) remained unvaccinated. At multiple Cox regression analysis, the adjusted risk of primary COVID-19 events during the entire study period increased in employees aged 40–49 years (aHR = 1.65; 95% CI: 1.01; 2.71), females (aHR = 1.28; 95%CI: 1.12; 1.45), local police officers (aHR = 1.82; 95%CI: 1.50; 2.22) and nursery teachers (aHR = 1.27; 95%CI: 1.13; 1.43). However, whilst the risk of primary infections in police officers increased already during the Alpha transmission period (aHR = 6.82; 95%CI: 4.48; 10.40), progressively reducing across subsequent variants, for nursery teachers, it increased during the Delta wave (aHR = 2.42; 1.70; 3.44), reducing with Omicron (aHR = 1.23; 95%CI: 1.07; 1.40). Compared to unvaccinated colleagues, during the entire study period the risk of primary infections was significantly lower in employees immunized with three (aHR = 0.42; 95%CI: 0.36; 0.47) or four (aHR = 0.30; 95%CI: 0.23; 0.40) doses of COVID-19 vaccine, for a vaccine effectiveness (VE) of 58% and 70%, respectively. The protective effect of vaccination against primary infections was confirmed in the sub-group analysis by main pandemic waves, for a VE of 75% for one dose against 99% for two doses during the Alpha transmission period, slightly reducing to 59% and 70% in Delta time, respectively. During the Omicron wave, the risk of primary SARS-CoV-2 infections diminished significantly with three (aHR = 0.42; 95%CI: 0.36; 0.49) or four vaccine doses (aHR = 0.09; 95%CI: 0.05; 0.16), for a VE of 58% and 91%, respectively. Moreover, the risk of primary SARS-CoV-2 reinfections during the entire study period reduced with one (aHR = 0.47; 95%CI: 0.27; 0.82), two (aHR = 0.42; 95%CI: 0.30; 0.58), three (aHR = 0.32; 95%CI: 0.24; 0.44) or four vaccine doses (aHR = 0.14; 95%CI: 0.05; 0.46), for a VE of 53%, 58%, 68% and 86% against reinfections, respectively. No significant difference in VE was associated with heterologous versus homologous triple vaccination, both against primary infections or reinfections. Conclusions: Primary SARS-CoV-2 infections were more likely among nursery teachers and local police officers. The risk of both primary infections and reinfections reduced with higher number of doses of COVID-19 vaccine, regardless of the pandemic wave. Since city council civil servants were swab tested on demand or for contact tracing, the estimation of COVID-19 risk and VE largely missed aymptomatic SARS-CoV-2 infections. On the one hand, the present study confirmed the protective effect of COVID-19 vaccination against symptomatic SARS-CoV-2 infections; on the other hand, it highlighted not only the importance of continuous booster doses to keep up the humoral immunity over time but also the importance of updated vaccine formulations to prevent and control the spread of a highly mutable virus. Moreover, the protective effect of the first two doses against reinfections confirmed the efficacy of hybrid immunity during Omicron time.
]]>Vaccines doi: 10.3390/vaccines12030253
Authors: Arun Thachappully Remesh Kalichamy Alagarasu Santoshkumar Jadhav Meera Prabhakar Rajlakshmi Viswanathan
Background: Pertussis, or whooping cough, is a global public health concern. Pertussis vaccines have demonstrated good protection against Bordetella pertussis infections, but their effectiveness against Bordetella parapertussis remains debated due to conflicting study outcomes. Methods: A systematic review and meta-analysis were conducted to assess the effectiveness of pertussis vaccines in protecting children against B. parapertussis infection. A comprehensive search of PubMed, Web of Science, and Scopus databases was conducted, and randomized controlled trials (RCTs) and observational studies that met inclusion criteria were included in the analysis. Results: The meta-analysis, involving 46,533 participants, revealed no significant protective effect of pertussis vaccination against B. parapertussis infection (risk ratio: 1.10, 95% confidence interval: 0.83 to 1.44). Subgroup analyses by vaccine type and study design revealed no significant protection. The dearth of recent data and a limited pool of eligible studies, particularly RCTs, underscore a critical gap that warrants future research in the domain. Conclusions: These findings offer crucial insights into the lack of effectiveness of pertussis vaccines against B. parapertussis. Given the rising incidence of cases and outbreaks, coupled with the lack of cross-protection by the existing vaccines, there is an urgent need to develop vaccines that include specific antigens to protect against B. parapertussis.
]]>Vaccines doi: 10.3390/vaccines12030252
Authors: Minako Yamaoka-Tojo Taiki Tojo
Herpes zoster, induced by the reactivation of the varicella-zoster virus (VZV), is a unilaterally distributed vesicular rash that can cause multiple complications. VZV not only causes neurological problems, including postherpetic neuralgia and ocular zoster, but also causes inflammatory vasculopathy and increases the incidence of hemorrhagic or ischemic complications. Therefore, understanding the association between the development of herpes zoster and the subsequent occurrence of acute stroke or cardiovascular diseases, including myocardial infarction and heart failure, is of great interest. Conversely, many risk factors are involved in the development of herpes zoster. Recently, it has become clear that aging, insufficient immune function, and diseases related to lifestyle habits (for example, stroke and cardiovascular disease), can trigger the onset of herpes zoster. Preventing the onset of herpes zoster, which substantially reduces quality of life, will lead to lower medical costs for countries and extend healthy life expectancy for general populations. Thus, because herpes zoster is a vaccine-preventable disease, active vaccination is recommended for high-risk groups. This review summarizes the association between herpes zoster and cardiovascular disease and vaccination against herpes zoster as a useful disease management and prevention measure for cardiovascular disease.
]]>Vaccines doi: 10.3390/vaccines12030251
Authors: Yishu Fan Bo Xiao Mengqi Zhang
Vascular cognitive impairment (VCI) encompasses a wide range of cognitive disorders stemming from cerebrovascular issues, such as strokes or small vessel disease. These conditions often pose challenges to traditional diagnostic approaches due to their multifactorial nature and varied clinical presentations. Recently, next-generation sequencing (NGS) technologies have provided detailed analyses of long non-coding RNAs (lncRNAs) in the molecular pathobiology of VCI. These new findings help with molecular-based diagnostics and treatments of VCI. Within this realm, the concept of immune modulation, especially through specific vaccinations, emerges as a promising therapeutic strategy in VCI mitigation. In this review, we comprehensively elucidate the function of lncRNAs in VCI, emphasizing the advanced understanding of VCI’s molecular underpinnings made possible through NGS technologies. Significant focus is placed on the immune system’s role in VCI, particularly the neuroinflammatory processes which are consequential to cerebrovascular abnormalities. We believe that lncRNAs participate in regulating these immunological pathways, potentially guiding the development of vaccines targeting VCI. In this context, we propose a novel perspective: using knowledge about lncRNA profiles and functions to guide vaccine development, we can potentially exploit the body’s immune response to mitigate or prevent VCI. This approach has the potential to revolutionize VCI management by introducing targeted immunization strategies informed by molecular signatures, a concept that remains largely unexplored in current research endeavors. In addition, we summarize current progress and propose future directions, advocating for robust, interdisciplinary studies to validate the potential intersections between lncRNA landscapes, VCI pathology, and immunology. This review aims to spur innovative research and promote the development of lncRNA-informed vaccine strategies as proactive interventions against the cognitive consequences of VCI.
]]>Vaccines doi: 10.3390/vaccines12030250
Authors: Shunbin Ning Davide Firinu
The global vaccination campaign against SARS-CoV-2, the virus responsible for COVID-19, has been a monumental endeavor, marked by unprecedented collaboration between scientific researchers and pharmaceutical companies [...]
]]>Vaccines doi: 10.3390/vaccines12030249
Authors: Xiaoping Bian Jin Chen Xin Chen Chengying Liu Jianjun Ding Mengru Li Xiaofen Zhang Qing Liu Qingke Kong
The gram-negative facultative intracellular pathogen Salmonella enterica serotype Choleraesuis, also known as S. Choleraesuis, is a major financial loss for the pig business. C500 is a vaccine strain that has been used for preventing S. Choleraesuis infection in pigs for many years in China. Although it possessed good immunogenicity and protection efficacy, it still showed severe side effects. The truncation of the key gene rpoS in C500 was believed to take the major responsibility for its attenuation. To achieve a good balance between attenuation and immunogenicity, rpoS was restored to an active state, and other essential virulent genes of crp, fur, phoP, and aroA were evaluated for their effects of deletion on safety and immunogenicity. Animal experiments demonstrated that C5001 (C500 rpoS+ Δcrp10) and C5002 (C500 rpoS+ Δfur9) showed an excellent ability to induce an immune response. To further decrease the endotoxic activity, the combination mutations of ΔpagL7 ΔpagP81::Plpp lpxE ΔlpxR9 were introduced into the mutant strains to generate 1′-dephosphorylated lipid A. Animal experiments showed that SC3 (C500 rpoS+ Δfur9 ΔpagL7 ΔpagP81:: Plpp lpxE ΔlpxR9) induced higher levels of IgG and secreted IgA antibodies and provided a higher protection rate than SC1 (C500 ΔpagL7 ΔpagP81:: Plpp lpxE ΔlpxR9) and SC2 (C500 rpoS+ Δcrp10 ΔpagL7 ΔpagP81:: PlpplpxE ΔlpxR9). We also evaluated the ability of SC3 (C500 rpoS+ Δfur9 ΔpagL7 ΔpagP81:: Plpp lpxE ΔlpxR9) as a vaccine carrier to deliver heterologous protein antigens and polysaccharide antigens. The results indicated that SC3 (C500 rpoS+ Δfur9 ΔpagL7 ΔpagP81:: Plpp lpxE ΔlpxR9) showed an excellent ability to deliver heterologous antigens and induce the host to produce high levels of antibodies. Together, these results indicate that we constructed a safe and efficient attenuated strain of the S. Choleraesuis vaccine, which demonstrated strong resistance to infection with wild-type S. Choleraesuis and can be employed as a universal vector for the delivery of recombinant antigens.
]]>Vaccines doi: 10.3390/vaccines12030248
Authors: Susanne Herwig Julia M. Adler Daria Vladimirova Jakob Trimpert Jalid Sehouli Günter Cichon
During the COVID-19 pandemic, the early emergence of viral variants repeatedly undermined the effects of vaccination. Our aim here is to explore strategies for improving spike vaccine gene antigenicity by merging mutations from different variants of concern (VOCs) in a single vaccine gene. To this end, newly developed recombinant vaccine genes were designed, cloned into adenoviral vectors, and applied to C57BL/6 mice; then, serum-neutralizing antibodies against the wildtype SARS-CoV-2 strains were determined in neutralization assays. The merger of mutations from different variants of concern (alpha, beta, gamma, and delta) in a single recombinant spike-based vaccine gene provided a substantial improvement in neutralizing immunity to all variants of concern, including the omicron strains. To date, only unmodified spike genes of the original SARS-CoV-2 Wuhan strain (B.1) or dominant variants (BA.1, BA.5, and XBB.1.5) have been used as vaccine genes. The employment of unmodified vaccine genes is afflicted by limited cross-protection among variant strains. In contrast, recombinant vaccine genes that combine mutations from different strains in a single gene hold the potential to broaden and improve immune protection and might help to reduce the need for frequent vaccine adaptations in the future.
]]>Vaccines doi: 10.3390/vaccines12030247
Authors: Nina Ekström Tuija M. Leino Aapo Juutinen Toni Lehtonen Anu Haveri Oona Liedes Saimi Vara Heini Salo Arto A. Palmu Hanna Nohynek Timi Martelius Merit Melin
Data on immune responses following COVID-19 booster vaccinations and subsequent infections in the immunocompromised are limited. We studied antibody responses after the fourth dose and subsequent infections to define patient groups benefiting most from boosters. Fourth vaccine (booster) doses were, in Finland, first recommended for severely immunocompromised individuals, whom we invited to participate in our study in 2022. We assessed spike protein-specific IgG and neutralizing antibodies (NAb) against the ancestral and Omicron BA.1 strains one month after the fourth dose from 488 adult participants and compared them to the levels of 35 healthy controls after three doses. We used Bayesian generalized linear modeling to assess factors explaining antibody levels and assessed vaccine-induced and hybrid immunity six months after the last vaccine dose. Chronic kidney disease (CKD) and immunosuppressive therapy (IT) were identified as factors explaining sub-optimal antibody responses. The proportion of participants with a normal antibody response and NAbs was significantly lower regarding CKD patients compared to the controls. By the 6-month sampling point, one-third of the participants became infected (documented by serology and/or molecular tests), which notably enhanced antibody levels in most immunocompromised participants. Impaired antibody responses, especially NAbs against the Omicron lineage, suggest limited protection in individuals with CKD and highlight the need for alternative pharmaceutical preventive strategies. Vaccination strategies should take into account the development of robust hybrid immunity responses also among the immunocompromised.
]]>Vaccines doi: 10.3390/vaccines12030246
Authors: Megan Halbrook Adva Gadoth Patrick Mukadi Nicole A. Hoff Kamy Musene Camille Dzogang Cyrus Shannon Sinai D’Andre Spencer Guillaume Ngoie-Mwamba Sylvia Tangney Frank Salet Michel Nyembwe Michel Kambamba Nzaji Merly Tambu Placide Mbala Trevon Fuller Sue K. Gerber Didine Kaba Jean Jacques Muyembe-Tamfum Anne W. Rimoin
Despite the successes in wild-type polio eradication, poor vaccine coverage in the DRC has led to the occurrence of circulating vaccine-derived poliovirus outbreaks. This cross-sectional population-based survey provides an update to previous poliovirus-neutralizing antibody seroprevalence studies in the DRC and quantifies risk factors for under-immunization and parental knowledge that guide vaccine decision making. Among the 964 children between 6 and 35 months in our survey, 43.8% (95% CI: 40.6–47.0%), 41.1% (38.0–44.2%), and 38.0% (34.9–41.0%) had protective neutralizing titers to polio types 1, 2, and 3, respectively. We found that 60.7% of parents reported knowing about polio, yet 25.6% reported knowing how it spreads. Our data supported the conclusion that polio outreach efforts were successfully connecting with communities—79.4% of participants had someone come to their home with information about polio, and 88.5% had heard of a polio vaccination campaign. Additionally, the odds of seroreactivity to only serotype 2 were far greater in health zones that had a history of supplementary immunization activities (SIAs) compared to health zones that did not. While SIAs may be reaching under-vaccinated communities as a whole, these results are a continuation of the downward trend of seroprevalence rates in this region.
]]>Vaccines doi: 10.3390/vaccines12030245
Authors: Denny Fe G. Agana-Norman Monica Martinez Martinez Manjushree Shanmugasundaram Abbey B. Berenson
HPV vaccination rates remain low among US adolescents, with only 54% completing the series in 2019. The vaccine is recommended at age 11–12 but can be given as early as age 9. Although it has been found that offering the vaccine earlier improves completion rates by age 13, parents remain reluctant to allow their younger children to initiate this vaccine. The purpose of this study was to better understand parental beliefs regarding receipt of the HPV vaccine among their children at ages 9–10. A 40 min phone interview was completed with 21 participants who were asked about their vaccine viewpoints. Even after receiving one-on-one education from a patient navigator, many caretakers expressed inadequate knowledge of the HPV vaccine and limited exposure to both positive and negative influences. The biggest concern was vaccine side effects, often resulting from a lack of medical understanding. Most parents were reluctant to vaccinate their children at a school-based clinic or pharmacy and believed that the government should not mandate HPV vaccination for public school attendance. Our study provides insight into parental beliefs and attitudes about HPV vaccination at age 9–10 years and barriers that need to be addressed.
]]>Vaccines doi: 10.3390/vaccines12030244
Authors: Jihane Belayachi Abdelkader Mhayi Hind Majidi Elmostafa El Fahime Redouane Abouqal
Objective: This study investigates the effectiveness of the 1st booster dose against COVID-19 severe and critical hospitalizations and deaths occurring due to the Omicron wave in Morocco. Participants/methods: This study uses nationally representative data on COVID-19 from 15 December 2021 to 31 January 2022. The aim is to investigate the effectiveness of the inactivated COVID-19 vaccine BBIBP-CorV (Sinopharm) 1st booster dose against the Omicron wave in Morocco using real-world data established from nationally representative statistics on COVID-19 cases, deaths and vaccinations. Statistical Analyses: The screening method was used to estimate vaccine effectiveness against COVID-19 severe or critical hospitalization and COVID-19-related deaths. The data were grouped by, age subgroup, sex, week, and geographical area and were analyzed using binary logistic regression with an offset for vaccine coverage. Results: The overall BBIBP-CorV VE estimate is 89% (95% CI 85 to 92) effective in curbing COVID-19 deaths, and 81% (95% CI 78 to 84 in curbing COVID-19 severe/critical hospitalizations. Death-related VE estimate was 86% (95% CI 81 to 90) for patients aged ≥65 years, 96% (95% CI 90 to 98) for those aged <65 years, 95% (95% CI 88 to 98) in no-risk factor patients, 91% (95% CI 85 to 94) with 1 risk factor, 90% (95% CI 83 to 95) with 2 risk factors, and 72% (95% CI 52 to 84) in patients with 3 risk factors and more. Severe/critical hospitalization VE estimate was 78% (95% CI 74 to 82) for patients aged ≥65 years, 87% (95% CI 82 to 90) for those aged <65 years, 86% (95% CI 80 to 90) in no-risk factor patients, 80% (95% CI 73 to 84) with 1 risk factor, 80% (95% CI 70 to 85) with 2 risk factors, and 80% (95% CI 68 to 86) in patients with 3 risk factors and more. Conclusions: BBIBP-CorV boosters are effective in increasing protection against the Omicron variant-related COVID-19 deaths and severe/critical hospitalizations. The protection is reduced with older age and higher risk factors. These findings emphasize the importance of targeted vaccination strategies for different demographic groups and underscore the protective benefits of the first booster BBIBP-CorV vaccine.
]]>Vaccines doi: 10.3390/vaccines12030243
Authors: Delaram Doroud Fatemeh Ashrafian Amir Javadi Sarah Dahmardeh Mohammad Banifazl Anahita Bavand Mona Sadat Larijani Amitis Ramezani
PastoCovac is a subunit protein vaccine against COVID-19 which contains the tetanus toxoid as a carrier conjugated to SARS-CoV-2 RBD. The primary goal of the tetanus application was to elicit a stronger specific response in the individuals. However, conjugate vaccines have the potency to generate anticarrier antibodies in addition to the target antigen. Therefore, the present study aimed to evaluate the PastoCovac vaccine in the humoral immune induction against tetanus. Six groups of individuals, including those who received one, two, or three doses of the PastoCovac vaccine, Td vaccine, and also the controls who received other COVID-19 vaccines (except PastoCovac), were investigated. The anti-tetanus IgG was assessed by an ELISA assay in all vaccinated groups. The antibody persistency against tetanus in the group who received one dose of the PastoCovac vaccine was also assessed on day 60, 90, and 180 after the last injection. The anti-tetanus antibody titer in the three groups of PastoCovac recipients was positive, though additional doses of the vaccine led to a significant antibody rise (p = 0.003). Notably, the comparison of the mean antibody titer between the Td recipients and those who received one/two doses of PastoCovac showed that the mean rise in the antibody titer before and after the injection was not significant. Although the antibody titer on day 180 decreased to a lower level than on day 21, it was still estimated to be highly positive against tetanus. Eventually, none of the PastoCovac recipients presented vaccine side-effects during the follow-up. The current data indicate that the tetanus conjugate vaccine against COVID-19, PastoCovac, could induce immune responses against tetanus, which can persist for at least 6 months. Combination vaccine formulae containing TT and DT as carriers for conjugate vaccines could be considered instead of TT and/or DT boosters in adults if they are indicated.
]]>Vaccines doi: 10.3390/vaccines12030242
Authors: Aubrey G. Specht Melanie Ginese Sherry L. Kurtz Karen L. Elkins Harrison Specht Gillian Beamer
Mycobacterium bovis Bacillus Calmette-Guérin (BCG) protects against childhood tuberculosis; and unlike most vaccines, BCG broadly impacts immunity to other pathogens and even some cancers. Early in the COVID-19 pandemic, epidemiological studies identified a protective association between BCG vaccination and outcomes of SARS-CoV-2, but the associations in later studies were inconsistent. We sought possible reasons and noticed the study populations often lived in the same country. Since individuals from the same regions can share common ancestors, we hypothesized that genetic background could influence associations between BCG and SARS-CoV-2. To explore this hypothesis in a controlled environment, we performed a pilot study using Diversity Outbred mice. First, we identified amino acid sequences shared by BCG and SARS-CoV-2 spike protein. Next, we tested for IgG reactive to spike protein from BCG-vaccinated mice. Sera from some, but not all, BCG-vaccinated Diversity Outbred mice contained higher levels of IgG cross-reactive to SARS-CoV-2 spike protein than sera from BCG-vaccinated C57BL/6J inbred mice and unvaccinated mice. Although larger experimental studies are needed to obtain mechanistic insight, these findings suggest that genetic background may be an important variable contributing to different associations observed in human randomized clinical trials evaluating BCG vaccination on SARS-CoV-2 and COVID-19.
]]>Vaccines doi: 10.3390/vaccines12030241
Authors: Francesco Ciccimarra Nicoletta Luxi Chiara Bellitto Luca L’Abbate Monika Raethke Florence van Hunsel Thomas Lieber Erik Mulder Fabio Riefolo Caroline Dureau-Pournin Andreea Farcas Francisco Batel Marques Kathryn Morton Debabrata Roy Simona Sonderlichová Nicolas H. Thurin Felipe Villalobos Miriam C. Sturkenboom Gianluca Trifirò
In all pivotal trials of COVID-19 vaccines, the history of previous SARS-CoV-2 infection was mentioned as one of the main exclusion criteria. In the absence of clinical trials, observational studies are the primary source for evidence generation. This study aims to describe the patient-reported adverse drug reactions (ADRs) following the first COVID-19 vaccination cycle, as well as the administration of booster doses of different vaccine brands, in people with prior SARS-CoV-2 infection, as compared to prior infection-free matched cohorts of vaccinees. A web-based prospective study was conducted collecting vaccinee-reported outcomes through electronic questionnaires from eleven European countries in the period February 2021–February 2023. A baseline questionnaire and up to six follow-up questionnaires collected data on the vaccinee’s characteristics, as well as solicited and unsolicited adverse reactions. Overall, 3886 and 902 vaccinees with prior SARS-CoV-2 infection and having received the first dose or a booster dose, respectively, were included in the analysis. After the first dose or booster dose, vaccinees with prior SARS-CoV-2 infection reported at least one ADR at a higher frequency than those matched without prior infection (3470 [89.6%] vs. 2916 [75.3%], and 614 [68.2%] vs. 546 [60.6%], respectively). On the contrary side, after the second dose, vaccinees with a history of SARS-CoV-2 infection reported at least one ADR at a lower frequency, compared to matched controls (1443 [85.0%] vs. 1543 [90.9%]). The median time to onset and the median time to recovery were similar across all doses and cohorts. The frequency of adverse reactions was higher in individuals with prior SARS-CoV-2 infection who received Vaxzevria as the first dose and Spikevax as the second and booster doses. The frequency of serious ADRs was low for all doses and cohorts. Data from this large-scale prospective study of COVID-19 vaccinees could be used to inform people as to the likelihood of adverse effects based on their history of SARS-CoV-2 infection, age, sex, and the type of vaccine administered. In line with pivotal trials, the safety profile of COVID-19 vaccines was also confirmed in people with prior SARS-CoV-2 infection.
]]>Vaccines doi: 10.3390/vaccines12030240
Authors: Pere Godoy Iván Martínez-Baz Ignasi Parron Manuel García-Cenoz Joaquim Ferras Mònica Carol Nuria Bes Montserrat Guillaumes Sofia Godoy Diana Toledo Núria Follia Carme Miret Jessica Pardos Miquel Alsedà Pedro Plans-Rubio Inma Sanz Maria-Rosa Sala Joan A. Caylà Jacobo Mendioroz Carmen Muñoz-Almagro Jesús Castilla Ángela Domínguez on behalf of the SARS-CoV-2 Transmission to Household Contacts Working Group on behalf of the SARS-CoV-2 Transmission to Household Contacts Working Group
The aim of this study was to evaluate the impact of index case vaccination on SARS-CoV-2 transmission to household contacts. In our epidemiological cohort study (May 2022–November 2023), we surveyed registered index case vaccination status and test results for contacts (testing on day 0, and on day 7 for negative contacts) and calculated the secondary attack rate (SAR), i.e., newly infected contacts/susceptible included contacts. The association of the independent variable, index case COVID-19 vaccination (yes/no), with household contact infection was determined using the adjusted odds ratio (aOR) and its 95% confidence interval (CI). We recorded 181 index cases and 314 contacts, of whom 250 agreed to participate; 16 contacts were excluded upon testing positive on day 0. Of the 234 included contacts, 49.1% were women, and the mean (SD) age was 51.9 (19.8) years. The overall SAR of 37.2% (87/234) was lower in the contacts of both vaccinated index cases (34.9% vs. 63.2%; p = 0.014) and index cases with a previous SARS-CoV-2 infection history (27.0% vs. 46.3%; p = 0.002). Index case vaccination showed a protective effect against infection for their household contacts (aOR = 0.21; 95% CI: 0.07, 0.67). The household SAR was high when the Omicron variant circulated. Vaccinated index cases were less likely to transmit SARS-CoV-2 to their contacts.
]]>Vaccines doi: 10.3390/vaccines12030239
Authors: Valeria Asato Ravit Bassal Shiri Meron-Sudai Sophy Goren Lital Keinan-Boker Calman A. MacLennan Dani Cohen
Background: Shigella is a leading cause of moderate-to-severe diarrhea globally, with young children most affected. The burden of shigellosis drops increasingly with age, inferring the acquisition of natural immunity. We tested the hypothesis that IgG antibodies elicited against Shigella O-specific polysaccharide (O-SP) are correlates of age-acquired immunity. Objectives: We examined levels and determinants of serum IgG to S. sonnei LPS and the association with the incidence of S. sonnei shigellosis in Israeli children and adolescents. Methods: We analyzed 1096 serum samples from 0- to 19-year-olds collected in 2008–2015 for IgG anti-S. sonnei LPS levels by ELISA. Corresponding age-specific incidences of culture-proven S. sonnei shigellosis from 2008 to 2015 were obtained. We compared ecologically IgG levels, prevalence above a proposed protective threshold, and S. sonnei shigellosis incidence. Results: In a multivariable analysis model, children aged 1–4, 5–14, and 15–19 years were 6.71, 27.68, and 48.62 times more likely to have IgG anti-S. sonnei LPS above the threshold than those aged < 1 year, respectively (p < 0.001). Infants 0–3 months old had relatively high IgG anti-S. sonnei LPS levels of maternal origin that dropped thereafter. Children of low socioeconomic status had a 2.73 times higher likelihood of having IgG anti-S. sonnei LPS above the threshold (p < 0.001). A significant inverse correlation between age-specific IgG anti-S. sonnei LPS levels and S. sonnei shigellosis incidence was observed (Spearman rho= −0.76, p = 0.028). Conclusions: The study results support anti-S. sonnei LPS antibodies as correlates of protection that can inform Shigella vaccine development.
]]>Vaccines doi: 10.3390/vaccines12030238
Authors: Ines Aguinaga-Ontoso Sara Guillén-Aguinaga Laura Guillén-Aguinaga Rosa Alas-Brun Enrique Aguinaga-Ontoso Esperanza Rayón-Valpuesta Francisco Guillén-Grima
Background: In the Americas, deaths by diseases avoidable with vaccines are a significant contributor to child mortality. An essential means of reducing this is through broad vaccine coverage. The COVID-19 pandemic has posed a potential disruption to vaccine coverage due to its effects on the healthcare system. Objectives: this study aims to evaluate the impact of the COVID-19 pandemic on DTP3 vaccination coverage in the Americas, investigating trends from 2012 to 2022 to identify significant changes, regional disparities, and the overall effect of the pandemic on progress towards global immunization targets. Methods: This study used the coverage data for the third dose of the diphtheria, tetanus, and pertussis vaccine (DTP3) pulled from UNICEF databases spanning 2012 to 2022. We conducted a Joinpoint regression to identify points of significant trend changes. The annual percentage change (APC) and 95% confidence intervals (95% CIs) were calculated for America and its regions. We also used segmented regression analysis. Using the Chi-square test, we compared DTP3 vaccination coverage for each country between 2019 and 2022. Results: Overall, America saw a decrease in vaccine coverage during this period, with an APC of −1.4 (95% CI −1.8; −1.0). This trend varied across regions. In North America, the decrease was negligible (−0.1% APC). South America showed the steepest decrease, with an APC of −2.5%. Central America also declined, with an APC of −1.3%. Our findings suggest a concerning trend of declining DTP-vaccination rates in the Americas, exacerbated in certain regions, in the wake of the COVID-19 pandemic. The absolute decrease in vaccine coverage in the Americas was −4% between 2019 and 2022, with the most important drop being in Central America (−7%). However, six countries reported increased vaccination rates post-COVID-19, led by Brazil, with a 7% increase. Conversely, twenty-two countries registered a decline in DTP3 vaccine coverage, with the average decrease being −7.37%. This decline poses an important challenge to achieving the WHO’s target of 90% coverage for the third dose of DTP by 2030, as evidenced by the reduction in the number of countries meeting this target from 2019 to 2022. Conclusions: The COVID-19 pandemic has impacted vaccine coverage in America, leading to a decrease, especially across Central America.
]]>Vaccines doi: 10.3390/vaccines12030237
Authors: Dorien De Pooter Wim Pierson Soheil Pourshahian Koen Dockx Ben De Clerck Isabel Najera Heather Davis Ellen Van Gulck Daniel Boden
Chronic infection with hepatitis B virus (HBV) develops in millions of patients per year, despite the availability of effective prophylactic vaccines. Patients who resolve acute HBV infection develop HBV-specific polyfunctional T cells accompanied by neutralizing antibodies, while in patients with chronic hepatitis B (CHB), immune cells are dysfunctional and impaired. We describe a lipid nanoparticle (LNP)-formulated mRNA vaccine, optimized for the expression of HBV core, polymerase, and surface (preS2-S) antigens with the aim of inducing an effective immune response in patients with CHB. Prime and prime/boost vaccination with LNP-formulated mRNA encoding for core, pol, and/or preS2-S dosing strategies were compared in naive C57BL/6 and BALB/c mice. Immune responses were assessed by IFN-γ ELISpot, intracellular cytokine staining (ICS), and ELISA for antibody production, whereas anti-viral efficacy was evaluated in the AAV-HBV mouse model. The mRNA vaccine induced strong antigen-specific polyfunctional T cell responses in these mouse models, accompanied by the emergence of anti-HBs and anti-HBe antibodies. After three immunizations, the antigen-specific immune stimulation resulted in up to 1.7 log10 IU/mL reduction in systemic HBV surface antigen (HBsAg), accompanied by a transient drop in systemic HBeAg, and this was observed in 50% of the AAV-HBV-transduced mice in the absence of additional modalities such as adjuvants, HBsAg reducing agents, or checkpoint inhibitors. However, no treatment-related effect on viremia was observed in the liver. These results warrant further optimization and evaluation of this mRNA vaccine as a candidate in a multimodal therapeutic regimen for the treatment of chronic HBV infection.
]]>Vaccines doi: 10.3390/vaccines12030236
Authors: Vinícius Pinto Costa Rocha Bruna Aparecida Souza Machado Helenita Costa Quadros Antônio Márcio Santana Fernandes Bianca Sampaio Dotto Fiuza Cássio Santana Meira Vitória Torres Barbosa da Silva Afrânio Ferreira Evangelista Larissa Moraes dos Santos Fonseca Roberto José da Silva Badaró Milena Botelho Pereira Soares
The COVID-19 pandemic and the consequent emergence of new SARS-CoV-2 variants of concern necessitates the determination of populational serum potency against the virus. Here, we standardized and validated an imaging-based method to quantify neutralizing antibodies against lentiviral particles expressing the spike glycoprotein (pseudovirus). This method was found to efficiently quantify viral titers based on ZsGreen-positive cells and detect changes in human serum neutralization capacity induced by vaccination with up to two doses of CoronaVac, Comirnaty, or Covishield vaccines. The imaging-based protocol was also used to quantify serum potency against pseudoviruses expressing spikes from Delta, Omicron BA.1.1.529, and BA.4/5. Our results revealed increases in serum potency after one and two doses of the vaccines evaluated and demonstrated that Delta and Omicron variants escape from antibody neutralization. The method presented herein represents a valuable tool for the screening of antibodies and small molecules capable of blocking viral entry and could be used to evaluate humoral immunity developed by different populations and for vaccine development.
]]>Vaccines doi: 10.3390/vaccines12030235
Authors: Sara Properzi Maria Stella Sepioni Roberta Carestia Giulia Cervelli Chiara de Waure
Pregnant women and infants inherently face heightened susceptibility to complications resulting from infectious diseases. Within these populations, vaccinations offer numerous advantages. This systematic review endeavors to comprehensively analyze the existing literature concerning interventions designed to promote vaccinations among pregnant women and newborns in Italy. We searched PubMed, Scopus, and Web of Science for primary studies published until 3 August 2023 which assessed the impact of vaccination education interventions targeting pregnant Italian women. Data extraction, pooling, and a quality appraisal of the included studies were conducted according to PRISMA guidelines. Among the 528 articles identified, 3 met the inclusion criteria and focused on pregnant women aged 25 to 40 attending pre-delivery courses. In these studies, the effectiveness of the interventions was assessed using pre- and post-intervention questionnaires that investigated knowledge, attitudes, and behaviors regarding recommended vaccinations. The results reveal significant increases in intention and adherence to vaccination among participants after these interventions. The results underscore the positive influence of health professionals’ educational initiatives on pregnant Italian women’s vaccination knowledge and attitudes. However, longitudinal studies with larger representative samples are needed to validate these findings and identify potential avenues for improving maternal educational interventions.
]]>Vaccines doi: 10.3390/vaccines12030234
Authors: Philip O. Buck Dumingu Aparna Gomes Ekkehard Beck Noam Kirson Matthew Mattera Stuart Carroll Bernhard Ultsch Kavisha Jayasundara Mathieu Uhart Louis P. Garrison, Jr.
The COVID-19 pandemic’s dramatic impact has been a vivid reminder that vaccines—especially in the context of infectious respiratory viruses—provide enormous societal value, well beyond the healthcare system perspective which anchors most Health Technology Assessment (HTA) and National Immunization Technical Advisory Group (NITAG) evaluation frameworks. Furthermore, the development of modified ribonucleic acid-based (mRNA-based) and nanoparticle vaccine technologies has brought into focus several new value drivers previously absent from the discourse on vaccines as public health interventions such as increased vaccine adaptation capabilities, the improved ability to develop combination vaccines, and more efficient vaccine manufacturing and production processes. We review these novel value dimensions and discuss how they might be measured and incorporated within existing value frameworks using existing methods. To realize the full potential of next-generation vaccine platforms and ensure their widespread availability across populations and health systems, it is important that value frameworks utilized by HTAs and NITAGs properly reflect the full range of benefits for population health and well-being and cost efficiencies that these new vaccines platforms provide.
]]>Vaccines doi: 10.3390/vaccines12030233
Authors: Kaiyi Han Zhiyuan Hou Shiyi Tu Mengyun Liu Tracey Chantler Heidi Larson
Childhood influenza vaccination coverage remains low in lower/middle-income countries. This systematic review aims to identify influencing factors around childhood influenza vaccination. A systematic literature review was conducted and included empirical studies with original data that investigated factors influencing childhood influenza vaccination. We searched MEDLINE, Web of Science, EMBASE, CINAHL Plus, Global Health, PsycINFO, and two Chinese databases, China Knowledge Resource Integrated Database and Chongqing VIP, using a combination of the key terms ‘childhood’, ‘influenza’, ‘vaccination’, and related syntax for all peer-reviewed publications published before December 2019. Thirty studies were included in the analysis. Childhood influenza vaccination was positively associated with caregivers’ knowledge of influenza vaccine, positive vaccine attitudes, self-efficacy, perceived susceptibility and severity of influenza, believing in the efficacy of influenza vaccine, the worry of getting sick, healthcare workers’ recommendations, and previous influenza vaccination experiences. Barriers included the fear of safety and side effects of the vaccine, as well as poor access to vaccination service. To improve childhood influenza vaccine uptake, health education is necessary to address caregivers’ lack of confidence on vaccine safety. Future studies are needed to investigate influencing factors around healthcare workers’ vaccination recommendation behaviors and the impact of contextual factors on public vaccination behaviors.
]]>Vaccines doi: 10.3390/vaccines12030232
Authors: Yingying Wang Michelle L. Giles Natalie Carvalho
Maternal influenza immunisation (MII) is recommended for protecting pregnant women and infants under six months of age from severe disease related to influenza. However, few low-income countries have introduced this vaccine. Existing cost-effectiveness studies do not consider potential vaccine non-specific effects (NSE) observed in some settings, such as reductions in preterm birth. A decision tree model was built to examine the potential cost-effectiveness of MII in a hypothetical low-income country compared to no vaccination, considering possible values for NSE on preterm birth in addition to vaccine-specific effects on influenza. We synthesized epidemiological and cost data from low-income countries. All costs were adjusted to 2021 United States dollars (USD). We considered cost-effectiveness thresholds that reflect opportunity costs (USD 188 per disability-adjusted life year averted; range: USD 28–538). Results suggest that even a small (5%) NSE on preterm birth may make MII a cost-effective strategy in these settings. A value of information analysis indicated that acquiring more information on the presence and possible size of NSE of MII could greatly reduce the uncertainty in decision-making on MII. Further clinical research investigating NSE in low-income countries may be of high value to optimise immunisation policy.
]]>Vaccines doi: 10.3390/vaccines12030230
Authors: Sara Caldrer Silvia Accordini Cristina Mazzi Natalia Tiberti Michela Deiana Andrea Matucci Eleonora Rizzi Stefano Tais Fabio Filippo Matteo Verzè Paolo Cattaneo Gian Paolo Chiecchi Concetta Castilletti Massimo Delledonne Federico Gobbi Chiara Piubelli
Background: Currently approved vaccines are highly effective in protecting against hospitalization and severe COVID-19 infections. How pre-existing immunity responds to new variants with mutated antigens is crucial information for elucidating the functional interplay between antibodies and B and T cell responses during infection with new SARS-CoV-2 variants. Methods: In this study, we monitored the dynamics and persistence of the immune response versus different SARS-CoV-2 variants of concern that emerged during the pandemic period (2021–2022) in a cohort of vaccinated healthcare workers, who experienced breakthrough infection in the Pre-Delta, Delta, and Omicron waves. We evaluated both the humoral and cell-mediated responses after infection. We also evaluated the anti-SARS-CoV-2 antibodies levels produced by infection in comparison with those produced after vaccination. Results: Our results highlighted that the immune response against the Delta VOC mainly involved an adaptive humoral and switched memory B cells component, even 3 months after the last vaccine dose, conversely showing a high percentage of depleted adaptive T cells. Omicron infections triggered a consistent production of non-vaccine-associated anti-N antibodies, probably to balance the spike epitope immune escape mechanisms. Conclusion: Our results suggest a direct dependence between the VOC and different humoral and B and T cell balances in the post-infection period, despite the administration of a different number of vaccine doses and the elapsed time since the last vaccination.
]]>Vaccines doi: 10.3390/vaccines12030231
Authors: Dohyun Kim Sun Young Park Gyeongmin Lee Eun-Sol Kim Jong-Sook Jin Jae Young Kim SooAh Lee Jong-Hyeon Park Young-Joon Ko
Foot-and-mouth disease (FMD) is a highly contagious viral infection causing acute and severe vesicular lesions in cattle and pigs, which has prompted global vaccination policies. This study presents a technique for enhancing antigen yield in SAT1 BOT and SAT3 ZIM by treatment with calcium chloride (CaCl2). We tested changes in cell viability in BHK-21 suspension cells treated with varying concentrations of CaCl2. The optimal CaCl2 concentration was determined based on antigen yield. The timing of CaCl2 supplementation relative to FMD virus inoculation was tested. Finally, the optimal medium for antigen production was identified. We observed a concentration-dependent decrease in BHK-21 cell viability at >7.5 mM CaCl2. A CaCl2 concentration of 3 mM yielded the most antigens. CaCl2 supplementation relative to FMD virus infection was optimal 2 h before or with viral inoculation. CD-BHK 21 medium supplemented with CaCl2 was the most productive medium. Specifically, SAT1 BOT and SAT3 ZIM showed improved antigen production in CD-BHK 21 medium with 3 mM CaCl2, while Provero-1 and Cellvento BHK-200 media showed no significant enhancement. Overall, CaCl2 supplementation enhanced FMD antigen productivity. This study provides a useful framework for enhancing antigen production efficiently in the FMD vaccine industry.
]]>Vaccines doi: 10.3390/vaccines12030229
Authors: Pia Gattinger Bernhard Kratzer Al Nasar Ahmed Sehgal Anna Ohradanova-Repic Laura Gebetsberger Gabor Tajti Margarete Focke-Tejkl Mirjam Schaar Verena Fuhrmann Lukas Petrowitsch Walter Keller Sandra Högler Hannes Stockinger Winfried F. Pickl Rudolf Valenta
Background: COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a recurrent endemic disease affecting the whole world. Since November 2021, Omicron and its subvariants have dominated in the spread of the disease. In order to prevent severe courses of disease, vaccines are needed to boost and maintain antibody levels capable of neutralizing Omicron. Recently, we produced and characterized a SARS-CoV-2 vaccine based on a recombinant fusion protein consisting of hepatitis B virus (HBV)-derived PreS and two SARS-CoV-2 wild-type RBDs. Objectives: To develop a PreS-RBD vaccine which induces high levels of Omicron-specific neutralizing antibodies. Methods: We designed, produced, characterized and compared strain-specific (wild-type: W-PreS-W; Omicron: O-PreS-O), bivalent (mix of W-PreS-W and O-PreS-O) and chimeric (i.e., W-PreS-O) SARS-CoV-2 protein subunit vaccines. Immunogens were characterized in vitro using protein chemical methods, mass spectrometry, and circular dichroism in combination with thermal denaturation and immunological methods. In addition, BALB/c mice were immunized with aluminum–hydroxide-adsorbed proteins and aluminum hydroxide alone (i.e., placebo) to study the specific antibody and cytokine responses, safety and Omicron neutralization. Results: Defined and pure immunogens could be produced in significant quantities as secreted and folded proteins in mammalian cells. The antibodies induced after vaccination with different doses of strain-specific, bivalent and chimeric PreS-RBD fusion proteins reacted with wild-type and Omicron RBD in a dose-dependent manner and resulted in a mixed Th1/Th2 immune response. Interestingly, the RBD-specific IgG levels induced with the different vaccines were comparable, but the W-PreS-O-induced virus neutralization titers against Omicron (median VNT50: 5000) were seven- and twofold higher than the W-PreS-W- and O-PreS-O-specific ones, respectively, and they were six-fold higher than those of the bivalent vaccine. Conclusion: Among the tested immunogens, the chimeric PreS-RBD subunit vaccine, W-PreS-O, induced the highest neutralizing antibody titers against Omicron. Thus, W-PreS-O seems to be a highly promising COVID-19 vaccine candidate for further preclinical and clinical evaluation.
]]>Vaccines doi: 10.3390/vaccines12030228
Authors: Florica Șandru Andreea-Maria Radu Aida Petca Mihai Cristian Dumitrașcu Răzvan-Cosmin Petca Alexandra-Maria Roman
Human papillomavirus (HPV) encompasses a diverse array of viruses, comprising approximately 200 serotypes that affect humans. While the majority of HPV strains are associated with benign skin or mucous membrane growths, a subset is implicated in severe health conditions, such as cervical, anal, vulvar, and vaginal cancers. Despite the established effectiveness of HPV vaccines in preventing cervical and anal carcinomas in particular, their therapeutic potential in addressing cutaneous diseases linked to diverse HPV strains remains an intriguing area of investigation. This narrative review critically examines the existing literature to assess the viability of HPV immunization as a therapeutic intervention for prevalent cutaneous conditions. These include genital and extragenital cutaneous warts, epidermodysplasia verruciformis, and keratinocyte carcinomas. The findings suggest a promising dual role for HPV vaccines in preventing and treating dermatologic conditions while emphasizing future research directions, including the immunization perspective against β-HPVs. Moreover, the presence of conflicting study outcomes underscores the imperative for larger-scale, randomized trials with well-matched control groups to validate the efficacy of HPV immunization in the dermatologic context. This review contributes valuable insights into the evolving landscape of HPV-vaccine applications in the field of dermatology.
]]>Vaccines doi: 10.3390/vaccines12030227
Authors: Henhen Heryaman Cep Juli Arnengsih Nazir Mas Rizky A. A. Syamsunarno Badrul Hisham Yahaya Dewi Kartika Turbawaty Rini Mulia Sari Hikmat Permana Rudi Supriyadi Nur Atik
Patients with Type 2 diabetes mellitus (T2DM) and Chronic Kidney Disease (CKD) face an increased risk of morbidity and mortality after influenza infection. Several studies have shown that the influenza vaccine effectively prevents morbidity and mortality in T2DM patients. However, there has been limited research aimed at assessing the effectiveness of the trivalent influenza vaccine in T2DM–CKD patients. This study aimed to identify Geometric Mean Titers (GMTs), seroprotection, seroconversion, safety, and efficacy. This open-label clinical trial was conducted at AMC Hospital in Bandung, West Java, Indonesia between June 2021 and July 2022. The study subjects consisted of 41 T2DM and 26 T2DM–CKD patients who were administered the trivalent influenza vaccine. There was a significant difference in the average age, with the T2DM–CKD patients being older. Median titers post-vaccination for the B/Washington virus were higher in the T2DM patients compared to the T2DM–CKD patients, and this difference was statistically significant. A majority, comprising 75.6% of the T2DM and 80.8% of the T2DM–CKD patients monitored post-influenza-vaccination, did not experience any adverse reactions. The most common reaction was the sensation of fever, with incidence rates of 12.2% in the T2DM patients and 15.4% in the T2DM–CKD patients. Furthermore, we observed that the incidence of Influenza-like Illness was highest at 7.3% in the T2DM patients and 7.7% in the T2DM–CKD patients. The trivalent influenza vaccine demonstrated equivalent safety and effectiveness in both groups.
]]>Vaccines doi: 10.3390/vaccines12030226
Authors: Jun-Feng Zhang Jong-Yeol Park Sang-Won Kim Yu-Ri Choi Se-Yeoun Cha Hyung-Kwan Jang Bai Wei Min Kang
Infectious bursal disease (IBD), caused by IBD virus (IBDV), is an extremely contagious immunosuppressive disease that causes major losses for the poultry industry worldwide. Recently, the novel variant IBDV (G2d) has been highly prevalent in Korea, but the current vaccines against this very virulent IBDV have limited efficacy against this novel variant. To develop a vaccine against this variant IBDV, a recombinant virus designated rHVT-VP2 was constructed by inserting the IBDV (G2d) VP2 gene into herpesvirus of turkeys (HVT) using CRISPR/Cas9 gene-editing technology. The PCR and sequencing results obtained showed that the recombinant virus rHVT-VP2 was successfully constructed. Vaccination with rHVT-VP2 generated IBDV-specific antibodies in specific pathogen-free chickens starting from 2 weeks post-immunization. Seven days after the challenge, the autopsy results showed that the bursa atrophy rates of the rHVT-VP2, HVT, vaccine A, and positive control groups were 0%, 100%, 60%, and 100%, respectively, and the BBIX values were 1.07 ± 0.22, 0.27 ± 0.05, 0.64 ± 0.33, and 0.32 ± 0.06, respectively. These results indicate that rHVT-VP2 can provide 100% protection against a challenge with the IBDV (G2d), whereas vaccine A only provides partial protection. In conclusion, vaccination with the recombinant virus rHVT-VP2 can provide chickens with effective protection against variant IBDV (G2d).
]]>Vaccines doi: 10.3390/vaccines12030225
Authors: Michiko Toizumi Lien Thuy Le Hien Anh Thi Nguyen Thao Thi Thu Le Noriko Kitamura Liem Xuan Bui Nen Minh Ho Hung Thai Do Kazunari Kamachi Nao Otsuka Minh Xuan Bui Duc Anh Dang Lay-Myint Yoshida
The underestimation of the pertussis burden prompted our study to investigate the prevalence of recent pertussis infection, its associated factors, and antibody titer changes in the same individuals in Vietnam. Two cross-sectional surveys were conducted in Nha Trang in 2017 and Quang Ngai in 2019, representing high- and low-vaccine-coverage areas, respectively. Serum anti-pertussis toxin immunoglobulin-G (anti-PT IgG) ≥ 62.5 IU/mL by ELISA indicated infection in the previous 12 months. In Nha Trang, the participants of the 2017 survey were followed up in 2019. Logistic regression was used to determine the odds ratios for the characteristics associated with anti-PT IgG ≥ 62.5. The age-stratified prevalence in patients aged >2 years ranged from 2.1% (age 26–35) to 9.6% (3–5) in Nha Trang (2017) and from 7.2% (age 26–35) to 11.4% (6–15) in Quang Ngai. The prevalence tended to be higher in Quang Ngai across all age groups. Cough, recent antibiotic use, and smoking in Nha Trang were positively associated with an anti-PT IgG of ≥62.5, and having been diagnosed with pertussis and persistent cough with paroxysms/whoop in Quang Ngai were positively associated with an anti-PT IgG of ≥62.5. No nasopharyngeal swabs were positive for Bordetella pertussis using real-time PCR. The geometric mean of the IgG titer ratio from 2019 to 2017 was 1.45 in the paired samples. This study emphasizes Bordetella pertussis circulation across all age groups in both low- and high-vaccine-coverage settings in Vietnam, underscoring the need for continuous and standardized surveillance for a comprehensive understanding of its epidemiology.
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