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Vaccines, Volume 12, Issue 4 (April 2024) – 103 articles

Cover Story (view full-size image): Vaccination is the most effective measure against influenza. Healthcare workers (HCWs) are considered a priority group for receiving this vaccine, but historically they have been reticent. The COVID-19 pandemic has heightened awareness of its importance. This study investigated the trends of vaccination coverage (VC) among HCWs from the 2019/2020 to 2022/2023 seasons, potential factors influencing HCWs acceptance, and the occurrence of adverse events (AE). Our findings reveal an increase in VC during the most critical moments of the pandemic (2020/21 and 2021/22 seasons), which has, subsequently, decreased (2022/2023 season) to levels below pre-pandemic (2019/2020 season). The most frequent reason for vaccination was “self-protection”, and 26.6% reported at least one AE, but none were severe, which justifies implementing specific measures to recover the VC. View this paper
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12 pages, 238 KiB  
Article
COVID-19 Vaccine Hesitancy and Associated Oral Cholera Vaccine Hesitancy in a Cholera-Endemic Country: A Community-Based Cross-Sectional Study in the Democratic Republic of Congo
by Arsene Daniel Nyalundja, Patrick Musole Bugeme, Alain Balola Ntaboba, Victoire Urbain Hatu’m, Guillaume Shamamba Ashuza, Jacques Lukenze Tamuzi, Duduzile Ndwandwe, Chinwe Iwu-Jaja, Charles Shey Wiysonge and Patrick D. M. C. Katoto
Vaccines 2024, 12(4), 444; https://doi.org/10.3390/vaccines12040444 - 22 Apr 2024
Viewed by 745
Abstract
COVID-19 vaccine hesitancy and its enablers shape community uptake of non-covid vaccines such as the oral cholera vaccine (OCV) in the post-COVID-19 era. This study assessed the impact of COVID-19 vaccine hesitancy and its drivers on OCV hesitancy in a cholera-endemic region of [...] Read more.
COVID-19 vaccine hesitancy and its enablers shape community uptake of non-covid vaccines such as the oral cholera vaccine (OCV) in the post-COVID-19 era. This study assessed the impact of COVID-19 vaccine hesitancy and its drivers on OCV hesitancy in a cholera-endemic region of the Democratic Republic of Congo. We conducted a community-based survey in Bukavu. The survey included demographics, intention to take OCV and COVID-19 vaccines, reasons for COVID-19 hesitancy, and thoughts and feelings about COVID-19 vaccines. Poisson regression analyses were performed. Of the 1708 respondents, 84.66% and 77.57% were hesitant to OCV alone and to both OCV and COVID-19, respectively. Hesitancy to COVID-19 vaccines rose OCV hesitancy by 12% (crude prevalence ratio, [cPR] = 1.12, 95%CI [1.03–1.21]). Independent predictors of OCV hesitancy were living in a semi-urban area (adjusted prevalence ratio [aPR] = 1.10, 95%CI [1.03–1.12]), religious refusal of vaccines (aPR = 1.06, 95%CI [1.02–1.12]), concerns about vaccine safety (aPR = 1.05, 95%CI [1.01–1.11]) and adverse effects (aPR = 1.06, 95%CI [1.01–1.12]), as well as poor vaccine literacy (aPR = 1.07, 95%CI [1.01–1.14]). Interestingly, the belief in COVID-19 vaccine effectiveness reduced OCV hesitancy by 24% (aPR = 0.76, 95%CI [0.62–0.93]). COVID-19 vaccine hesitancy and its drivers exhibited a significant domino effect on OCV uptake. Addressing vaccine hesitancy through community-based health literacy and trust-building interventions would likely improve the introduction of novel non-COVID-19 vaccines in the post-COVID-19 era. Full article
(This article belongs to the Special Issue 50 Years of Immunization—Steps Forward)
22 pages, 3402 KiB  
Article
Characterization of the Protective Cellular Immune Response in Pigs Immunized Intradermally with the Live Attenuated African Swine Fever Virus (ASFV) Lv17/WB/Rie1
by Miriam Pedrera, Alejandro Soler, Alicia Simón, Nadia Casado, Covadonga Pérez, María A. García-Casado, Paloma Fernández-Pacheco, Pedro J. Sánchez-Cordón, Marisa Arias and Carmina Gallardo
Vaccines 2024, 12(4), 443; https://doi.org/10.3390/vaccines12040443 - 20 Apr 2024
Viewed by 872
Abstract
Candidate vaccines against African swine fever virus (ASFV) based on naturally attenuated or genetically modified viruses have the potential to generate protective immune responses, although there is no consensus on what defines a protective immune response against ASFV. Studies, especially in sensitive host [...] Read more.
Candidate vaccines against African swine fever virus (ASFV) based on naturally attenuated or genetically modified viruses have the potential to generate protective immune responses, although there is no consensus on what defines a protective immune response against ASFV. Studies, especially in sensitive host species and focused on unravelling protective mechanisms, will contribute to the development of safer and more effective vaccines. The present study provides a detailed analysis of phenotypic and functional data on cellular responses induced by intradermal immunization and subsequent boosting of domestic pigs with the naturally attenuated field strain Lv17/WB/Rie1, as well as the mechanisms underlying protection against intramuscular challenge with the virulent genotype II Armenia/07 strain. The transient increase in IL-8 and IL-10 in serum observed after immunization might be correlated with survival. Protection was also associated with a robust ASFV-specific polyfunctional memory T-cell response, where CD4CD8 and CD8 T cells were identified as the main cellular sources of virus-specific IFNγ and TNFα. In parallel with the cytokine response, these T-cell subsets also showed specific cytotoxic activity as evidenced by the increased expression of the CD107a degranulation marker. Along with virus-specific multifunctional CD4CD8 and CD8 T-cell responses, the increased levels of antigen experienced in cytotoxic CD4 T cells observed after the challenge in immunized pigs might also contribute to controlling virulent infection by killing mechanisms targeting infected antigen-presenting cells. Future studies should elucidate whether the memory T-cell responses evidenced in the present study persist and provide long-term protection against further ASFV infections. Full article
(This article belongs to the Special Issue Diagnosis and Control of African Swine Fever Virus (ASFV) Infection)
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14 pages, 273 KiB  
Article
Anti-Herpes Zoster Vaccination of Fragile Patients in Hospital Setting: A Nudge Intervention in Italy
by Francesco De Caro, Francesca Malatesta, Nadia Pecoraro, Mario Capunzo, Luna Carpinelli, Simona Caruccio, Giuseppina Cersosimo, Maria Costantino, Claudio Giordano, Walter Longanella, Vincenzo Patella, Arcangelo Saggese Tozzi, Giulia Savarese, Pio Sinopoli, Emilia Anna Vozzella and Giuseppina Moccia
Vaccines 2024, 12(4), 442; https://doi.org/10.3390/vaccines12040442 - 19 Apr 2024
Viewed by 694
Abstract
Background: A nudge intervention against Herpes Zoster, created and implemented in Italy, is presented in order to administer the Shingrix vaccine on a sample of frail patients, as required by the National Prevention Plan. Individual and contextual factors associated with vaccine adherence were [...] Read more.
Background: A nudge intervention against Herpes Zoster, created and implemented in Italy, is presented in order to administer the Shingrix vaccine on a sample of frail patients, as required by the National Prevention Plan. Individual and contextual factors associated with vaccine adherence were investigated. Method: 300 frail adult subjects underwent a full vaccine cycle with recombinant-Shingrix vaccine (RZV vaccine). Hospital Presidia of the Salerno University Hospital Authority, a Hospital Presidium of the Salerno Local Health Authority, and the Public Health Laboratory of the University of Salerno (Campania) participated in the intervention. An ad hoc questionnaire was administered with the following scales: EQ-5D, PSS-10, MSPSS, and representations of HZ and its consequences. Results: Some variables, such as peer support, doctor–patient relationship, level of education, and perception of health, are important in vaccine adherence and information processing. The following factors emerged from the factor analysis: Trust in collective knowledge and collective responsibility (F1); beliefs about virus risk and vaccine function (F2); information about virus and symptomatology (F3); and vaccine distrust (F4). Factor 4 correlates negatively with social support indices (R = −0.363; p < 0.001). There is a significant relationship between factor 3 and satisfaction with national information campaigns (F = 3.376; gdl = 5; p-value = 0.006). Conclusions: Future vaccination campaigns should be built with the aim of personalizing information and developing contextualized strategies, starting from understanding the stakeholders involved, cultural contexts, and organizational settings. Full article
(This article belongs to the Special Issue Vaccination Uptake and Public Health)
21 pages, 4222 KiB  
Article
The Papain-like Protease Domain of Severe Acute Respiratory Syndrome Coronavirus 2 Conjugated with Human Beta-Defensin 2 and Co1 Induces Mucosal and Systemic Immune Responses against the Virus
by Byeol-Hee Cho, Ju Kim and Yong-Suk Jang
Vaccines 2024, 12(4), 441; https://doi.org/10.3390/vaccines12040441 - 19 Apr 2024
Viewed by 918
Abstract
Most of the licensed vaccines against SARS-CoV-2 target spike proteins to induce viral neutralizing antibodies. However, currently prevalent SARS-CoV-2 variants contain many mutations, especially in their spike proteins. The development of vaccine antigens with conserved sequences that cross-react with variants of SARS-CoV-2 is [...] Read more.
Most of the licensed vaccines against SARS-CoV-2 target spike proteins to induce viral neutralizing antibodies. However, currently prevalent SARS-CoV-2 variants contain many mutations, especially in their spike proteins. The development of vaccine antigens with conserved sequences that cross-react with variants of SARS-CoV-2 is needed to effectively defend against SARS-CoV-2 infection. Given that viral infection is initiated in the respiratory mucosa, strengthening the mucosal immune response would provide effective protection. We constructed a mucosal vaccine antigen using the papain-like protease (PLpro) domain of non-structural protein 3 of SARS-CoV-2. To potentiate the mucosal immune response, PLpro was combined with human beta-defensin 2, an antimicrobial peptide with mucosal immune adjuvant activity, and Co1, an M-cell-targeting ligand. Intranasal administration of the recombinant PLpro antigen conjugate into C57BL/6 and hACE2 knock-in (KI) mice induced antigen-specific T-cell and antibody responses with complement-dependent cytotoxic activity. Viral challenge experiments using the Wuhan and Delta strains of SARS-CoV-2 provided further evidence that immunized hACE2 KI mice were protected against viral challenge infections. Our study shows that PLpro is a useful candidate vaccine antigen against SARS-CoV-2 infection and that the inclusion of human beta-defensin 2 and Co1 in the recombinant construct may enhance the efficacy of the vaccine. Full article
(This article belongs to the Section Vaccine Adjuvants)
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16 pages, 271 KiB  
Article
Courage in Decision Making: A Mixed-Methods Study of COVID-19 Vaccine Uptake in Women of Reproductive Age in the U.K.
by Laura A. Magee, Julia R. Brown, Vicky Bowyer, Gillian Horgan, Harriet Boulding, Asma Khalil, Nathan J. Cheetham, Nicholas R. Harvey, COVID Symptom Study Biobank Consortium, RESILIENT Study Group, Hiten D. Mistry, Carole Sudre, Sergio A. Silverio, Peter von Dadelszen and Emma L. Duncan
Vaccines 2024, 12(4), 440; https://doi.org/10.3390/vaccines12040440 - 18 Apr 2024
Viewed by 877
Abstract
COVID-19 vaccination rates are lower in women of reproductive age (WRA), including pregnant/postpartum women, despite their poorer COVID-19-related outcomes. We evaluated the vaccination experiences of 3568 U.K. WRA, including 1983 women (55.6%) experiencing a pandemic pregnancy, recruited through the ZOE COVID Symptom Study [...] Read more.
COVID-19 vaccination rates are lower in women of reproductive age (WRA), including pregnant/postpartum women, despite their poorer COVID-19-related outcomes. We evaluated the vaccination experiences of 3568 U.K. WRA, including 1983 women (55.6%) experiencing a pandemic pregnancy, recruited through the ZOE COVID Symptom Study app. Two staggered online questionnaires (Oct–Dec 2021: 3453 responders; Aug–Sept 2022: 2129 responders) assessed reproductive status, COVID-19 status, vaccination, and attitudes for/against vaccination. Descriptive analyses included vaccination type(s), timing relative to age-based eligibility and reproductive status, vaccination delay (first vaccination >28 days from eligibility), and rationale, with content analysis of free-text comments. Most responders (3392/3453, 98.2%) were vaccinated by Dec 2021, motivated by altruism, vaccination supportiveness in general, low risk, and COVID-19 concerns. Few declined vaccination (by Sept/2022: 20/2129, 1.0%), citing risks (pregnancy-specific and longer-term), pre-existing immunity, and personal/philosophical reasons. Few women delayed vaccination, although pregnant/postpartum women (vs. other WRA) received vaccination later (median 3 vs. 0 days after eligibility, p < 0.0001). Despite high uptake, concerns included adverse effects, misinformation (including from healthcare providers), ever-changing government advice, and complex decision making. In summary, most women in this large WRA cohort were promptly vaccinated, including pregnant/post-partum women. Altruism and community benefit superseded personal benefit as reasons for vaccination. Nevertheless, responders experienced angst and received vaccine-related misinformation and discouragement. These findings should inform vaccination strategies in WRA. Full article
22 pages, 1254 KiB  
Review
Hepatitis B Vaccine: Four Decades on
by Maria Mironova and Marc G. Ghany
Vaccines 2024, 12(4), 439; https://doi.org/10.3390/vaccines12040439 - 18 Apr 2024
Viewed by 1072
Abstract
Hepatitis B virus is a substantial contributor to cirrhosis and hepatocellular carcinoma (HCC) globally. Vaccination is the most effective method for prevention of hepatitis B and its associated morbidity and mortality, and the only method to prevent infection with hepatitis D virus. The [...] Read more.
Hepatitis B virus is a substantial contributor to cirrhosis and hepatocellular carcinoma (HCC) globally. Vaccination is the most effective method for prevention of hepatitis B and its associated morbidity and mortality, and the only method to prevent infection with hepatitis D virus. The hepatitis B vaccine has been used worldwide for more than four decades; it is available in a single- or triple-antigen form and in combination with vaccines against other infections. Introduction of the vaccine and administration at birth led to sustained decline in mother-to-child transmission, chronic hepatitis B, and HCC, however, global birth dose coverage remains suboptimal. In this review we will discuss different hepatitis B vaccine formulations and schedules, vaccination guidelines, durability of the response, and vaccine escape mutants, as well as the clinical and economic benefits of vaccination. Full article
(This article belongs to the Special Issue Efficacy, Safety, and Immunogenicity of Hepatitis B Vaccines)
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12 pages, 3085 KiB  
Article
Using a Dynamic Model to Estimate the Cost-Effectiveness of HPV Vaccination in Iran
by Arnold Hagens, Albertus Constantijn Sloof and Roksana Janghorban
Vaccines 2024, 12(4), 438; https://doi.org/10.3390/vaccines12040438 - 18 Apr 2024
Viewed by 846
Abstract
This study aimed to determine the cost-effectiveness of vaccination against HPV. An age–sex structured dynamic disease transmission model was created to estimate the spread of HPV and the HPV-related incidence of cervical cancer (CC) in Iran. Sixteen age groups of men and women [...] Read more.
This study aimed to determine the cost-effectiveness of vaccination against HPV. An age–sex structured dynamic disease transmission model was created to estimate the spread of HPV and the HPV-related incidence of cervical cancer (CC) in Iran. Sixteen age groups of men and women were incorporated to reflect the differences in sexual preferences, vaccination uptake, and disease-related outcomes. Three scenarios were evaluated by using an Incremental Cost-Effectiveness Ratio (ICER) with gained quality-adjusted life years (QALYs). ICER values below one gross domestic product (GDP) per capita are evaluated as highly cost-effective. Vaccination reduces the number of infections and CC-related mortality. Over time, the vaccinated group ages and older age groups experience protection. An initial investment is required and savings in treatment spending reduce the impact over time. Vaccinating girls only was found to be cost-effective, with an ICER close to once the GDP per capita. Vaccinating both sexes was shown to be less cost-effective compared to girls only, and vaccinating boys only was not found to be cost-effective, with an ICER between once and three times, and greater than three times the GDP per capita, respectively. The estimates are conservative since societal cost-saving and the impact of other HPV-related illnesses were not considered and would likely reduce the ICERs. Full article
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15 pages, 2259 KiB  
Article
Analysis of Protection and Immune Response against Teladorsagia circumcincta in Goats Immunised with Thiol-Binding Proteins from Adult Worms
by Leire Ortega, Jessica Quesada, Antonio Ruiz, Magnolia María Conde-Felipe, Otilia Ferrer, María del Carmen Muñoz, José Adrián Molina, Francisco Rodríguez and José Manuel Molina
Vaccines 2024, 12(4), 437; https://doi.org/10.3390/vaccines12040437 - 18 Apr 2024
Viewed by 803
Abstract
In view of the increasing occurrence of anthelmintic-resistant strains of gastrointestinal nematodes in ruminants, various alternative control strategies have been investigated, such as those based on the induction of protective immune responses by immunisation with parasite antigens. In this study, the protective activity [...] Read more.
In view of the increasing occurrence of anthelmintic-resistant strains of gastrointestinal nematodes in ruminants, various alternative control strategies have been investigated, such as those based on the induction of protective immune responses by immunisation with parasite antigens. In this study, the protective activity of somatic antigens from adult worms of Teladorsagia circumcincta purified by affinity chromatography on thiol-sepharose was analysed in goats. After challenge, the enriched products induced a slight reduction in the cumulative faecal egg counts (21%) and in the number of worms (23.3%), with a greater effect on female worms, which also showed a reduction in parameters related to their fertility. These parasitological findings were associated with a Th2 immune response, with a prominent local humoral response and an eosinophilic infiltrate in the gastric mucosa (negatively associated with the fertility of female worms and the number of worms, respectively), as well as an infiltration of MCHII+, CD4+, IgG+ and IgA+ cells. However, several analyses showed an increase in CD8+ cells in the mucosa, as well as IL-2 expression in the gastric lymph nodes, which may have been associated with inhibition of protective responses or with the development of mixed Th1/Th2 responses, a finding that should be analysed in future studies. Full article
(This article belongs to the Special Issue Parasitic Infections: Therapy for Host Immunity and Vaccination)
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9 pages, 956 KiB  
Brief Report
Inactivated Split MERS-CoV Antigen Prevents Lethal Middle East Respiratory Syndrome Coronavirus Infections in Mice
by Heejeong Seo, Yunyueng Jang and Dongmi Kwak
Vaccines 2024, 12(4), 436; https://doi.org/10.3390/vaccines12040436 - 18 Apr 2024
Viewed by 959
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) causes fatal infections, with about 36% mortality in humans, and is endemic to the Middle East. MERS-CoV uses human dipeptidyl peptidase 4 (hDPP4) as a receptor for infection. Despite continued research efforts, no licensed vaccine is available [...] Read more.
Middle East respiratory syndrome coronavirus (MERS-CoV) causes fatal infections, with about 36% mortality in humans, and is endemic to the Middle East. MERS-CoV uses human dipeptidyl peptidase 4 (hDPP4) as a receptor for infection. Despite continued research efforts, no licensed vaccine is available for protection against this disease in humans. Therefore, this study sought to develop an inactivated fragmented MERS-CoV vaccine grown in Vero cells in an hDPP4-transgenic mouse model. Two-dose immunisation in mice with 15, 20, or 25 μg of spike proteins of inactivated split MERS-CoV antigens induced neutralising antibodies, with titres ranging from NT 80 to 1280. In addition, all immunised mice were completely protected, with no virus detection in tissues, weight loss, or mortality. The immunised splenocytes produced more cytokines that stimulate immune response (IFN-γ and TNF-α) than those that regulate it (IL-4 and IL-10). Taken together, the inactivated fragmented MERS-CoV vaccine is effective for the protection of mice against lethal MERS-CoV. Thus, the inactivated fragmented MERS-CoV vaccine warrants further testing in other hosts. Full article
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12 pages, 237 KiB  
Article
The Full Value of Vaccine Assessments Concept—Current Opportunities and Recommendations
by Richard G. White, Nicolas A. Menzies, Allison Portnoy, Rebecca A. Clark, Cristiana M. Toscano, Charlotte Weller, Marta Tufet Bayona, Sheetal Prakash Silal, Ruth A. Karron, Jung-Seok Lee, Jean-Louis Excler, Jeremy A. Lauer, Birgitte Giersing, Philipp Lambach, Raymond Hutubessy and Mark Jit
Vaccines 2024, 12(4), 435; https://doi.org/10.3390/vaccines12040435 - 18 Apr 2024
Viewed by 1095
Abstract
For vaccine development and adoption decisions, the ‘Full Value of Vaccine Assessment’ (FVVA) framework has been proposed by the WHO to expand the range of evidence available to support the prioritization of candidate vaccines for investment and eventual uptake by low- and middle-income [...] Read more.
For vaccine development and adoption decisions, the ‘Full Value of Vaccine Assessment’ (FVVA) framework has been proposed by the WHO to expand the range of evidence available to support the prioritization of candidate vaccines for investment and eventual uptake by low- and middle-income countries. Recent applications of the FVVA framework have already shown benefits. Building on the success of these applications, we see important new opportunities to maximize the future utility of FVVAs to country and global stakeholders and provide a proof-of-concept for analyses in other areas of disease control and prevention. These opportunities include the following: (1) FVVA producers should aim to create evidence that explicitly meets the needs of multiple key FVVA consumers, (2) the WHO and other key stakeholders should develop standardized methodologies for FVVAs, as well as guidance for how different stakeholders can explicitly reflect their values within the FVVA framework, and (3) the WHO should convene experts to further develop and prioritize the research agenda for outcomes and benefits relevant to the FVVA and elucidate methodological approaches and opportunities for standardization not only for less well-established benefits, but also for any relevant research gaps. We encourage FVVA stakeholders to engage with these opportunities. Full article
17 pages, 686 KiB  
Article
The Potential Economic Impact of the Updated COVID-19 mRNA Fall 2023 Vaccines in Japan
by Kelly Fust, Keya Joshi, Ekkehard Beck, Michael Maschio, Michele Kohli, Amy Lee, Yuriko Hagiwara, Nicolas Van de Velde and Ataru Igarashi
Vaccines 2024, 12(4), 434; https://doi.org/10.3390/vaccines12040434 - 18 Apr 2024
Viewed by 1004
Abstract
This analysis estimates the economic and clinical impact of a Moderna updated COVID-19 mRNA Fall 2023 vaccine for adults ≥18 years in Japan. A previously developed Susceptible-Exposed-Infected-Recovered (SEIR) model with a one-year analytic time horizon (September 2023–August 2024) and consequences decision tree were [...] Read more.
This analysis estimates the economic and clinical impact of a Moderna updated COVID-19 mRNA Fall 2023 vaccine for adults ≥18 years in Japan. A previously developed Susceptible-Exposed-Infected-Recovered (SEIR) model with a one-year analytic time horizon (September 2023–August 2024) and consequences decision tree were used to estimate symptomatic infections, COVID-19 related hospitalizations, deaths, quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratio (ICER) for a Moderna updated Fall 2023 vaccine versus no additional vaccination, and versus a Pfizer–BioNTech updated mRNA Fall 2023 vaccine. The Moderna vaccine is predicted to prevent 7.2 million symptomatic infections, 272,100 hospitalizations and 25,600 COVID-19 related deaths versus no vaccine. In the base case (healthcare perspective), the ICER was ¥1,300,000/QALY gained ($9400 USD/QALY gained). Sensitivity analyses suggest results are most affected by COVID-19 incidence, initial vaccine effectiveness (VE), and VE waning against infection. Assuming the relative VE between both bivalent vaccines apply to updated Fall 2023 vaccines, the base case suggests the Moderna version will prevent an additional 1,100,000 symptomatic infections, 27,100 hospitalizations, and 2600 deaths compared to the Pfizer–BioNTech vaccine. The updated Moderna vaccine is expected to be highly cost-effective at a ¥5 million willingness-to-pay threshold across a wide range of scenarios. Full article
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21 pages, 1610 KiB  
Article
Validation and Suitability Assessment of Multiplex Mesoscale Discovery Immunogenicity Assay for Establishing Serological Signatures Using Vaccinated, Non-Vaccinated and Breakthrough SARS-CoV-2 Infected Cases
by Sushant Shengule, Shweta Alai, Sachin Bhandare, Sumant Patil, Manish Gautam, Bhushan Mangaonkar, Sumit Gupta, Umesh Shaligram and Sunil Gairola
Vaccines 2024, 12(4), 433; https://doi.org/10.3390/vaccines12040433 - 18 Apr 2024
Viewed by 1001
Abstract
Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are multi-targeted and variable over time. Multiplex quantitative serological assays are needed to provide accurate and robust seropositivity data for the establishment of serological signatures during vaccination and or infection. We describe here [...] Read more.
Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are multi-targeted and variable over time. Multiplex quantitative serological assays are needed to provide accurate and robust seropositivity data for the establishment of serological signatures during vaccination and or infection. We describe here the validation and evaluation of an electro-chemiluminescence (ECL)-based Mesoscale Discovery assay (MSD) for estimation of total and functional IgG relative to SARS-CoV-2 spike, nucleocapsid and receptor binding (RBD) proteins in human serum samples to establish serological signatures of SARS-CoV-2 natural infection and breakthrough cases. The 9-PLEX assay was validated as per ICH, EMA, and US FDA guidelines using a panel of sera samples, including the NIBSC/WHO reference panel (20/268). The assay demonstrated high specificity and selectivity in inhibition assays, wherein the homologous inhibition was more than 85% and heterologous inhibition was below 10%. The assay also met predetermined acceptance criteria for precision (CV < 20%), accuracy (70–130%) and dilutional linearity. The method’s applicability to serological signatures was demonstrated using sera samples (n = 45) representing vaccinated, infected and breakthrough cases. The method was able to establish distinct serological signatures and thus provide a potential tool for seroprevalence of SARS-CoV-2 during vaccination or infection. Full article
(This article belongs to the Special Issue SARS-CoV-2 Serology for the Rapid Diagnosis of COVID-19)
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12 pages, 1754 KiB  
Article
Enhancement of SARS-CoV-2 mRNA Vaccine Efficacy through the Application of TMSB10 UTR for Superior Antigen Presentation and Immune Activation
by Xiaoyan Ding, Yuxin Zhou, Jiuxiang He, Jing Zhao and Jintao Li
Vaccines 2024, 12(4), 432; https://doi.org/10.3390/vaccines12040432 - 17 Apr 2024
Viewed by 752
Abstract
The development of effective vaccines against SARS-CoV-2 remains a critical challenge amidst the ongoing global pandemic. This study introduces a novel approach to enhancing mRNA vaccine efficacy by leveraging the untranslated region (UTR) of TMSB10, a gene identified for its significant mRNA abundance [...] Read more.
The development of effective vaccines against SARS-CoV-2 remains a critical challenge amidst the ongoing global pandemic. This study introduces a novel approach to enhancing mRNA vaccine efficacy by leveraging the untranslated region (UTR) of TMSB10, a gene identified for its significant mRNA abundance in antigen-presenting cells. Utilizing the GEO database, we identified TMSB10 among nine genes, with the highest mRNA abundance in dendritic cell subtypes. Subsequent experiments revealed that TMSB10’s UTR significantly enhances the expression of a reporter gene in both antigen-presenting and 293T cells, surpassing other candidates and a previously optimized natural UTR. A comparative analysis demonstrated that TMSB10 UTR not only facilitated a higher reporter gene expression in vitro but also showed marked superiority in vivo, leading to enhanced specific humoral and cellular immune responses against the SARS-CoV-2 Delta variant RBD antigen. Specifically, vaccines incorporating TMSB10 UTR induced significantly higher levels of specific IgG antibodies and promoted a robust T-cell immune response, characterized by the increased secretion of IFN-γ and IL-4 and the proliferation of CD4+ and CD8+ T cells. These findings underscore the potential of TMSB10 UTR as a strategic component in mRNA vaccine design, offering a promising avenue to bolster vaccine-induced immunity against SARS-CoV-2 and, potentially, other pathogens. Full article
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25 pages, 3170 KiB  
Article
Comparison of Wealth-Related Inequality in Tetanus Vaccination Coverage before and during Pregnancy: A Cross-Sectional Analysis of 72 Low- and Middle-Income Countries
by Nicole E. Johns, Cauane Blumenberg, Katherine Kirkby, Adrien Allorant, Francine Dos Santos Costa, M. Carolina Danovaro-Holliday, Carrie Lyons, Nasir Yusuf, Aluísio J. D. Barros and Ahmad Reza Hosseinpoor
Vaccines 2024, 12(4), 431; https://doi.org/10.3390/vaccines12040431 - 17 Apr 2024
Viewed by 701
Abstract
Immunization of pregnant women against tetanus is a key strategy for reducing tetanus morbidity and mortality while also achieving the goal of maternal and neonatal tetanus elimination. Despite substantial progress in improving newborn protection from tetanus at birth through maternal immunization, umbilical cord [...] Read more.
Immunization of pregnant women against tetanus is a key strategy for reducing tetanus morbidity and mortality while also achieving the goal of maternal and neonatal tetanus elimination. Despite substantial progress in improving newborn protection from tetanus at birth through maternal immunization, umbilical cord practices and sterilized and safe deliveries, inequitable gaps in protection remain. Notably, an infant’s tetanus protection at birth is comprised of immunization received by the mother during and before the pregnancy (e.g., through childhood vaccination, booster doses, mass vaccination campaigns, or during prior pregnancies). In this work, we examine wealth-related inequalities in maternal tetanus toxoid containing vaccination coverage before pregnancy, during pregnancy, and at birth for 72 low- and middle-income countries with a recent Demographic and Health Survey or Multiple Indicator Cluster Survey (between 2013 and 2022). We summarize coverage levels and absolute and relative inequalities at each time point; compare the relative contributions of inequalities before and during pregnancy to inequalities at birth; and examine associations between inequalities and coverage levels. We present the findings for countries individually and on aggregate, by World Bank country income grouping, as well as by maternal and neonatal tetanus elimination status, finding that most of the inequality in tetanus immunization coverage at birth is introduced during pregnancy. Inequalities in coverage during pregnancy are most pronounced in low- and lower-middle-income countries, and even more so in countries which have not achieved maternal and neonatal tetanus elimination. These findings suggest that pregnancy is a key time of opportunity for equity-oriented interventions to improve maternal tetanus immunization coverage. Full article
(This article belongs to the Special Issue Inequality in Immunization 2024)
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15 pages, 3867 KiB  
Article
STAT1-Deficient HPV E6/E7-Associated Cancers Maintain Host Immunocompetency against Therapeutic Intervention
by Ling Lim, Ming-Hung Hu, Darrell Fan, Hsin-Fang Tu, Ya-Chea Tsai, Michelle Cheng, Suyang Wang, Chih-Long Chang, Tzyy-Choou Wu and Chien-Fu Hung
Vaccines 2024, 12(4), 430; https://doi.org/10.3390/vaccines12040430 - 17 Apr 2024
Viewed by 812
Abstract
Human papillomavirus (HPV) remains a global health concern because it contributes to the initiation of various HPV-associated cancers such as anal, cervical, oropharyngeal, penile, vaginal, and vulvar cancer. In HPV-associated cancers, oncogenesis begins with an HPV infection, which is linked to the activation [...] Read more.
Human papillomavirus (HPV) remains a global health concern because it contributes to the initiation of various HPV-associated cancers such as anal, cervical, oropharyngeal, penile, vaginal, and vulvar cancer. In HPV-associated cancers, oncogenesis begins with an HPV infection, which is linked to the activation of the Janus protein tyrosine kinase (JAK)/STAT signaling pathway. Various STAT signaling pathways, such as STAT3 activation, have been well documented for their tumorigenic role, yet the role of STAT1 in tumor formation remains unclear. In the current study, STAT1−/− mice were used to investigate the role of STAT1 in the tumorigenesis of a spontaneous HPV E6/E7-expressing oral tumor model. Subsequently, our candidate HPV DNA vaccine CRT/E7 was administered to determine whether the STAT1−/− host preserves a therapeutic-responsive tumor microenvironment. The results indicated that STAT1−/− induces robust tumorigenesis, yet a controlled tumor response was attained upon CRT/E7 vaccination. Characterizing this treatment effect, immunological analysis found a higher percentage of circulating CD4+ and CD8+ T cells and tumor-specific cytotoxic T cells. In addition, a reduction in exhaustive lymphocyte activity was observed. Further analysis of a whole-cell tumor challenge affirmed these findings, as spontaneous tumor growth was more rapid in STAT1−/− mice. In conclusion, STAT1 deletion accelerates tumorigenesis, but STAT1−/− mice maintains immunocompetency in CRT/E7 treatments. Full article
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16 pages, 4297 KiB  
Article
The Association between Parental Child Vaccination Refusal Rate and the Impact of Mass Vaccination against COVID-19 in Kazakhstan: An Interrupted Time Series Analysis with Predictive Modelling of Nationwide Data Sources from 2013 to 2022
by Madina Abenova, Askhat Shaltynov, Ulzhan Jamedinova, Erlan Ospanov and Yuliya Semenova
Vaccines 2024, 12(4), 429; https://doi.org/10.3390/vaccines12040429 - 17 Apr 2024
Viewed by 679
Abstract
Despite well-established evidence supporting vaccination efficacy in reducing morbidity and mortality among infants and children, there is a global challenge with an increasing number of childhood vaccination refusals. This issue has intensified, especially during the COVID-19 pandemic. Our study aims to forecast mandatory [...] Read more.
Despite well-established evidence supporting vaccination efficacy in reducing morbidity and mortality among infants and children, there is a global challenge with an increasing number of childhood vaccination refusals. This issue has intensified, especially during the COVID-19 pandemic. Our study aims to forecast mandatory childhood vaccination refusal trends in Kazakhstan until 2030, assessing the impact of mass COVID-19 vaccination on these rates. Utilizing annual official statistical data from 2013 to 2022 provided by the Ministry of Health of Kazakhstan, the study reveals a significant surge in refusals during the pandemic and post-pandemic periods, reaching record levels of 42,282 cases in 2021 and 44,180 cases in 2022. Notably, refusal rates sharply rose in specific regions, like Aktobe (13.9 times increase) and Atyrau (4.29 times increase), emphasizing the need for increased public healthcare attention in these areas. However, despite a decade of data, our forecasting analysis indicates a lack of volatility in childhood vaccine refusal trends for all vaccine types up to 2030, highlighting the statistical significance of the obtained results. The increasing trend in vaccine refusals underscores the necessity to enhance crisis response and support health initiatives, particularly in regions where a substantial rise in refusals has been observed in recent years. Full article
(This article belongs to the Special Issue Vaccine Hesitancy)
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14 pages, 1698 KiB  
Systematic Review
Therapeutic Vaccines for HPV-Associated Cervical Malignancies: A Systematic Review
by Souhail Alouini and Chantal Pichon
Vaccines 2024, 12(4), 428; https://doi.org/10.3390/vaccines12040428 - 17 Apr 2024
Viewed by 1428
Abstract
Importance: Despite widespread prophylactic vaccination, cervical cancer continues to be a major health problem with considerable mortality. Currently, therapeutic vaccines for HPV-associated cervical malignancies are being evaluated as a potential complement to the standard treatment. Objective: The present systematic review was conducted on [...] Read more.
Importance: Despite widespread prophylactic vaccination, cervical cancer continues to be a major health problem with considerable mortality. Currently, therapeutic vaccines for HPV-associated cervical malignancies are being evaluated as a potential complement to the standard treatment. Objective: The present systematic review was conducted on randomized controlled trials (RCTs) to investigate the effects of therapeutic vaccines on the treatment of patients with cervical cancer and cervical intraepithelial neoplasia (CIN) of Grades 2 and 3. Evidence Review: The PubMed, Embase, and Cochrane Central Register of Controlled Trials databases were searched. Only articles in English published up until 31 January 2024 were selected. Also, reference lists of the selected original papers and recent review articles were manually searched for additional sources. Data on study characteristics were extracted from the selected articles. Data on outcomes of interest were synthesized, and vaccine efficacy endpoints (histological lesion regression, clinical response, and overall survival) were selected as the basis for grouping the studies. Findings: After screening 831 articles, nine RCTs with 800 participants were included, of which seven studies with 677 participants involved CIN2 and CIN3 and examined lesion regression to ≤CIN1 as the efficacy endpoint. Results of two of these studies were deemed to have a high risk of bias, and another one did not contain statistical analyses. Results of the other four studies were quantitively synthesized, and the pooling of p-values revealed a significant difference between the vaccine and placebo groups in terms of lesion regression (p-values of 0.135, 0.049, and 0.034 in RCTs, yielding a combined p-value of 0.010). The certainty of the evidence was rated as moderate. Patients with advanced cervical cancers were studied in two RCTs with 123 participants. Clinical response and overall survival were taken as endpoints, and the results were reported as not significant. The certainty of the evidence of these results was rated as very low, mainly due to the very small number of events. All studies reported good tolerance for the vaccines. Conclusions and Relevance: The results indicate the potential for therapeutic vaccines in the regression of CIN2 and CIN3 lesions. Moreover, a potential gap in evidence is identified regarding the very low number of RCTs in patients with advanced cervical cancer. Full article
(This article belongs to the Section Cancer Vaccines and Immunotherapy)
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12 pages, 261 KiB  
Article
Vaccination: Adherence and Hesitancy among Pregnant Women for COVID-19, Pertussis, and Influenza Vaccines
by Gabriele Filip, Alessia Sala, Veronica Modolo, Luca Arnoldo, Laura Brunelli and Lorenza Driul
Vaccines 2024, 12(4), 427; https://doi.org/10.3390/vaccines12040427 - 17 Apr 2024
Viewed by 788
Abstract
In the realm of antenatal care, vaccinations serve as a cornerstone, crucial for safeguarding the health of both the mother and the fetus, while also extending protection to the newborn against communicable diseases. Nevertheless, vaccine adherence among pregnant women remains very low. The [...] Read more.
In the realm of antenatal care, vaccinations serve as a cornerstone, crucial for safeguarding the health of both the mother and the fetus, while also extending protection to the newborn against communicable diseases. Nevertheless, vaccine adherence among pregnant women remains very low. The aim of our study was to evaluate the uptake of vaccines (influence, pertussis, and COVID-19) among women during pregnancy and to understand pregnant women’s knowledge of vaccines and the diseases they protect against. The purpose was to investigate the reasons why pregnant women chose not to be vaccinated and to develop effective strategies for informing them about the importance of vaccination for both maternal and fetal safety. A prospective observational study was conducted in the Department of Obstetrics and Gynaecology, “Ospedale Santa Maria della Misericordia” in Udine, from 1 December 2021 to 30 June 2022. During this period, a self-completed paper questionnaire was administered to women at the end of pregnancy or during the puerperium. A total of 161 questionnaires were collected. Higher educational level was found to be significantly associated with influenza vaccination uptake (p = 0.037, OR = 2.18, 95% CI 1.05–4.51). Similarly, for pertussis vaccination, adherence was mainly associated with higher educational level (p = 0.014, OR = 2.83, 95% CI 1.24–6.47), but also with Italian nationality (p = 0.003, OR = 3.36, 95% CI 1.56–8.43) and pregnancy attended by a midwife or private gynecologist (p = 0.028, OR = 0.39, 95% CI 0.17–0.90). Regarding the COVID-19 vaccine, the only factor positively influencing uptake was Italian nationality (p = 0.044, OR = 2.66, 95% CI 1.03–6.91). Women’s fear that vaccines would endanger the fetus appeared to be the most important reason for refusing vaccinations. Simultaneously, patients also exhibited a desire to receive more information about maternal vaccination, particularly from their general physician or gynecologist. For this reason, it is imperative to enhance maternal vaccination counselling, making it a routine step in prenatal care from the first antenatal visit until the postpartum period. Full article
9 pages, 989 KiB  
Brief Report
Binding of Natural Antibodies Generated after COVID-19 and Vaccination with Individual Peptides Corresponding to the SARS-CoV-2 S-Protein
by Anna M. Timofeeva, Sergey E. Sedykh, Ekaterina A. Litvinova, Sergey A. Dolgushin, Andrey L. Matveev, Nina V. Tikunova and Georgy A. Nevinsky
Vaccines 2024, 12(4), 426; https://doi.org/10.3390/vaccines12040426 - 17 Apr 2024
Viewed by 804
Abstract
The rapid development of vaccines is a crucial objective in modern biotechnology and molecular pharmacology. In this context, conducting research to expedite the selection of a potent immunogen is imperative. The candidate vaccine should induce the production of antibodies that can recognize the [...] Read more.
The rapid development of vaccines is a crucial objective in modern biotechnology and molecular pharmacology. In this context, conducting research to expedite the selection of a potent immunogen is imperative. The candidate vaccine should induce the production of antibodies that can recognize the immunogenic epitopes of the target protein, resembling the ones found in recovered patients. One major challenge in vaccine development is the absence of straightforward and reliable techniques to determine the extent to which the spectrum of antibodies produced after vaccination corresponds to antibodies found after recovery. This paper describes a newly developed method to detect antibodies specific to immunogenic epitopes of the target protein in blood plasma and to compare them with antibody spectra generated post vaccination. Comparing the antibody pool generated in the human body after recovering from an infectious disease with the pool formed through vaccination can become a universal method for screening candidate vaccines. This method will enable the identification of candidate vaccines that can induce the production of antibodies similar to those generated in response to a natural infection. Implementing this approach will facilitate the rapid development of new vaccines, even when faced with a pandemic. Full article
(This article belongs to the Special Issue Bioengineering in Vaccine Design and Delivery)
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15 pages, 1599 KiB  
Article
Effects of Influenza Vaccine on the Immune Responses to SARS-CoV-2 Vaccination
by A. Riccomi, C. M. Trombetta, M. Dorrucci, D. Di Placido, N. Sanarico, F. Farchi, R. Giuseppetti, U. Villano, C. Marcantonio, S. Marchi, A. Ciaramella, P. Pezzotti, E. Montomoli, C. Valdarchi, A. R. Ciccaglione and S. Vendetti
Vaccines 2024, 12(4), 425; https://doi.org/10.3390/vaccines12040425 - 17 Apr 2024
Viewed by 862
Abstract
A number of studies have suggested that influenza vaccination can provide protection against COVID-19, but the underlying mechanisms that could explain this association are still unclear. In this study, the effect of the 2021/2022 seasonal influenza vaccination on the immune response to the [...] Read more.
A number of studies have suggested that influenza vaccination can provide protection against COVID-19, but the underlying mechanisms that could explain this association are still unclear. In this study, the effect of the 2021/2022 seasonal influenza vaccination on the immune response to the booster dose of anti-SARS-CoV-2 vaccination was evaluated in a cohort of healthy individuals. A total of 113 participants were enrolled, 74 of whom had no prior COVID-19 diagnosis or significant comorbidities were considered for the analysis. Participants received the anti-influenza tetravalent vaccine and the booster dose of the anti-SARS-CoV-2 vaccine or the anti-SARS-CoV-2 vaccine alone. Blood was collected before and 4 weeks after each vaccination and 12 weeks after SARS-CoV-2 vaccination and analyzed for anti-flu and anti-spike-specific antibody titers and for in vitro influenza and SARS-CoV-2 neutralization capacity. Results indicated an increased reactivity in subjects who received both influenza and SARS-CoV-2 vaccinations compared to those who received only the SARS-CoV-2 vaccine, with sustained anti-spike antibody titers up to 12 weeks post-vaccination. Immune response to the influenza vaccine was evaluated, and individuals were stratified as high or low responders. High responders showed increased antibody titers against the SARS-CoV-2 vaccine both after 4 and 12 weeks post-vaccination. Conversely, individuals classified as low responders were less responsive to the SARS-CoV-2 vaccine. These data indicate that both external stimuli, such as influenza vaccination, and the host’s intrinsic ability to respond to stimuli play a role in the response to the vaccine. Full article
(This article belongs to the Special Issue The Recent Development of Influenza Vaccine)
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12 pages, 585 KiB  
Article
The Immunogenicity of Monovalent Oral Poliovirus Vaccine Type 1 (mOPV1) and Inactivated Poliovirus Vaccine (IPV) in the EPI Schedule of India
by Lalitendu Mohanty, T. Jacob John, Shailesh D. Pawar, Padmasani Venkat Ramanan, Sharad Agarkhedkar and Pradeep Haldar
Vaccines 2024, 12(4), 424; https://doi.org/10.3390/vaccines12040424 - 17 Apr 2024
Viewed by 875
Abstract
Background: In 2016, the Global Polio Eradication Initiative (GPEI) recommended the cessation of using type 2 oral poliovirus vaccine (OPV) and OPV, with countries having to switch from the trivalent to bivalent OPV (bOPV) with the addition of inactivated poliovirus vaccine (IPV) in [...] Read more.
Background: In 2016, the Global Polio Eradication Initiative (GPEI) recommended the cessation of using type 2 oral poliovirus vaccine (OPV) and OPV, with countries having to switch from the trivalent to bivalent OPV (bOPV) with the addition of inactivated poliovirus vaccine (IPV) in their routine immunization schedule. The current GPEI strategy 2022–2026 includes a bOPV cessation plan and a switch to IPV alone or a combination of vaccine schedules in the future. The focus of our study was to evaluate the immunogenicity of monovalent OPV type 1 (mOPV1) with IPV and IPV-only schedules. Methods: This was a three-arm, multi-center randomized–controlled trial conducted in 2016–2017 in India. Participants, at birth, were randomly assigned to the bOPV-IPV (Arm A) or mOPV1-IPV (Arm B) or IPV (Arm C) schedules. Serum specimens collected at birth and at 14, 18, and 22 weeks old were analyzed with a standard microneutralization assay for all the three poliovirus serotypes. Results: The results of 598 participants were analyzed. The type 1 cumulative seroconversion rates four weeks after the completion of the schedule at 18 weeks were 99.5% (97.0–99.9), 100.0% (97.9–100.0), and 96.0% (92.0–98.1) in Arms A (4bOPV + IPV), B (4mOPV1 + IPV), and C (3IPV), respectively. Type 2 and type 3 seroconversions at 18 weeks were 80.0% (73.7–85.1), 76.9% (70.3–82.4); 93.2% (88.5–96.1), 100.0% (98.0–100.0); and 81.9% (75.6–86.8), 99.4% (96.9–99.9), respectively, in the three arms. Conclusions: This study shows the high efficacy of different polio vaccines for serotype 1 in all three schedules. The type 1 seroconversion rate of mOPV1 is non-inferior to bOPV. All the vaccines provide high type-specific immunogenicity. The program can adopt the use of different vaccines or schedules depending on the epidemiology from time to time. Full article
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14 pages, 4236 KiB  
Article
A TriAdj-Adjuvanted Chlamydia trachomatis CPAF Protein Vaccine Is Highly Immunogenic in Pigs
by Jessica Proctor, Maria Stadler, Lizette M. Cortes, David Brodsky, Lydia Poisson, Volker Gerdts, Alex I. Smirnov, Tatyana I. Smirnova, Subarna Barua, Darren Leahy, Kenneth W. Beagley, Jonathan M. Harris, Toni Darville and Tobias Käser
Vaccines 2024, 12(4), 423; https://doi.org/10.3390/vaccines12040423 - 16 Apr 2024
Viewed by 865
Abstract
Chlamydia trachomatis (Ct) infections are the most common sexually transmitted infection (STI). Despite effective antibiotics for Ct, undetected infections or delayed treatment can lead to infertility, ectopic pregnancies, and chronic pelvic pain. Besides humans, chlamydia poses similar health challenges in [...] Read more.
Chlamydia trachomatis (Ct) infections are the most common sexually transmitted infection (STI). Despite effective antibiotics for Ct, undetected infections or delayed treatment can lead to infertility, ectopic pregnancies, and chronic pelvic pain. Besides humans, chlamydia poses similar health challenges in animals such as C. suis (Cs) in pigs. Based on the similarities between humans and pigs, as well as their chlamydia species, we use pigs as a large biomedical animal model for chlamydia research. In this study, we used the pig model to develop a vaccine candidate against Ct. The vaccine candidate consists of TriAdj-adjuvanted chlamydial-protease-like activity factor (CPAF) protein. We tested two weekly administration options—twice intranasal (IN) followed by twice intramuscular (IM) and twice IM followed by twice IN. We assessed the humoral immune response in both serum using CPAF-specific IgG (including antibody avidity determination) and also in cervical and rectal swabs using CPAF-specific IgG and IgA ELISAs. The systemic T-cell response was analyzed following in vitro CPAF restimulation via IFN-γ and IL-17 ELISpots, as well as intracellular cytokine staining flow cytometry. Our data demonstrate that while the IN/IM vaccination mainly led to non-significant systemic immune responses, the vaccine candidate is highly immunogenic if administered IM/IN. This vaccination strategy induced high serum anti-CPAF IgG levels with strong avidity, as well as high IgA and IgG levels in vaginal and rectal swabs and in uterine horn flushes. In addition, this vaccination strategy prompted a pronounced cellular immune response. Besides inducing IL-17 production, the vaccine candidate induced a strong IFN-γ response with CD4 T cells. In IM/IN-vaccinated pigs, these cells also significantly downregulated their CCR7 expression, a sign of differentiation into peripheral-tissue-homing effector/memory cells. Conclusively, this study demonstrates the strong immunogenicity of the IM/IN-administered TriAdj-adjuvanted Ct CPAF vaccine candidate. Future studies will test the vaccine efficacy of this promising Ct vaccine candidate. In addition, this project demonstrates the suitability of the Cs pre-exposed outbred pig model for Ct vaccine development. Thereby, we aim to open the bottleneck of large animal models to facilitate the progression of Ct vaccine candidates into clinical trials. Full article
(This article belongs to the Section Vaccines against Infectious Diseases)
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29 pages, 628 KiB  
Review
Perspectives in the Development of Tools to Assess Vaccine Literacy
by Luigi Roberto Biasio, Patrizio Zanobini, Chiara Lorini and Guglielmo Bonaccorsi
Vaccines 2024, 12(4), 422; https://doi.org/10.3390/vaccines12040422 - 16 Apr 2024
Viewed by 890
Abstract
Vaccine literacy (VL) is the ability to find, understand, and evaluate vaccination-related information to make appropriate decisions about immunization. The tools developed so far for its evaluation have produced consistent results. However, some dimensions may be underestimated due to the complexity of factors [...] Read more.
Vaccine literacy (VL) is the ability to find, understand, and evaluate vaccination-related information to make appropriate decisions about immunization. The tools developed so far for its evaluation have produced consistent results. However, some dimensions may be underestimated due to the complexity of factors influencing VL. Moreover, the heterogeneity of methods used in studies employing these tools hinders a comprehensive understanding of its role even more. To overcome these limitations, a path has been sought to propose new instruments. This has necessitated updating earlier literature reviews on VL and related tools, exploring its relationship with vaccine hesitancy (VH), and examining associated variables like beliefs, attitudes, and behaviors towards immunization. Based on the current literature, and supported by the re-analysis of a dataset from an earlier study, we propose a theoretical framework to serve as the foundation for creating future assessment tools. These instruments should not only evaluate the psychological factors underlying the motivational aspect of VL, but also encompass knowledge and competencies. The positioning of VL in the framework at the intersection between sociodemographic antecedents and attitudes, leading to behaviors and outcomes, explains why and how VL can directly or indirectly influence vaccination decisions by countering VH and operating at personal, as well as at organizational and community levels. Full article
(This article belongs to the Section Human Vaccines and Public Health)
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14 pages, 927 KiB  
Article
Impact of HPV Vaccination on the Incidence of High-Grade Cervical Intraepithelial Neoplasia (CIN2+) in Women Aged 20–25 in the Northern Part of Norway: A 15-Year Study
by Marte Pettersen Mikalsen, Gunnar Skov Simonsen and Sveinung Wergeland Sørbye
Vaccines 2024, 12(4), 421; https://doi.org/10.3390/vaccines12040421 - 16 Apr 2024
Cited by 1 | Viewed by 1304
Abstract
Background: Human papillomavirus (HPV), the most prevalent sexually transmitted infection globally, is a key risk factor for high-grade cervical lesions and cervical cancer. Since 2009, HPV vaccination has been part of the national immunization program for girls in 7th grade in Norway (women [...] Read more.
Background: Human papillomavirus (HPV), the most prevalent sexually transmitted infection globally, is a key risk factor for high-grade cervical lesions and cervical cancer. Since 2009, HPV vaccination has been part of the national immunization program for girls in 7th grade in Norway (women born 1997 and later). This study aimed to assess the impact of HPV vaccination on the incidence of high-grade cervical precursors (CIN2+) among women aged 20–25 in Troms and Finnmark over a 15-year period. Materials and Methods: In this time series study, we analyzed cervical screening data from 15,328 women aged 20–25 in Troms and Finnmark, collected between 2008 and 2022. Statistical methods, including linear and logistic regression, were employed to evaluate changes in cervical intraepithelial neoplasia grade 2 and worse (CIN2+) incidence and compare risks between vaccine-offered cohorts and pre-vaccine cohorts. Results: The incidence of CIN2+ initially increased from 31 cases per year in 2008 to 110 cases in 2018, then significantly decreased to 44 cases per year by 2022 (p < 0.01). Women in pre-vaccine cohorts had a substantially higher risk of CIN2+ (OR 9.02, 95% CI 5.9–13.8) and CIN3+ (OR 19.6, 95% CI 7.3–52.6). Notably, no vaccinated women with CIN2+ tested positive for HPV types 16 or 18. Furthermore, none of the 13 cervical cancer cases recorded during the study were from the vaccinated cohorts. Interpretation: The findings suggest a significant reduction in the incidence of high-grade cervical precursors following the introduction of the HPV vaccine in Norway’s national immunization program, highlighting its effectiveness in cervical cancer prevention among young women in Northern Norway. Full article
(This article belongs to the Special Issue Vaccination Progress in COVID-19 and HPV)
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13 pages, 277 KiB  
Review
Improving Influenza Vaccination Coverage in Patients with Cancer: A Position Paper from a Multidisciplinary Expert Group
by Paolo Bonanni, Michele Maio, Giordano D. Beretta, Giancarlo Icardi, Alessandro Rossi and Saverio Cinieri
Vaccines 2024, 12(4), 420; https://doi.org/10.3390/vaccines12040420 - 16 Apr 2024
Viewed by 1121
Abstract
Patients with cancer can be immunocompromised because of their disease and/or due to anticancer therapy. In this population, severe influenza virus infections are associated with an elevated risk of morbidity and mortality. Influenza vaccination is therefore highly recommended in cancer patients, including those [...] Read more.
Patients with cancer can be immunocompromised because of their disease and/or due to anticancer therapy. In this population, severe influenza virus infections are associated with an elevated risk of morbidity and mortality. Influenza vaccination is therefore highly recommended in cancer patients, including those receiving anticancer therapy. However, vaccination coverage remains far below the recommended target for vulnerable subjects. Six specialists in oncology, hematology, immunology, and public health/vaccinology convened with the objective of developing strategies, based on evidence and clinical experience, for improving influenza vaccination coverage in cancer patients. This viewpoint provides an overview of current influenza vaccination recommendations in cancer patients, discusses barriers to vaccination coverage, and presents strategies for overcoming said barriers. New immunization issues raised by the COVID-19 pandemic are also addressed. Future directions include improving public education on influenza vaccination, providing the media with accurate information, improving knowledge among healthcare professionals, improving access to vaccines for cancer patients, co-administration of the influenza and COVID-19 vaccines, increased collaboration between oncologists and other health professionals, increased accessibility of digital vaccination registries to specialists, shared information platforms, and promoting immunization campaigns by healthcare systems with the support of scientific societies. Full article
22 pages, 3003 KiB  
Article
The Memory-CD8+-T-Cell Response to Conserved Influenza Virus Epitopes in Mice Is Not Influenced by Time Since Previous Infection
by Josien Lanfermeijer, Koen van de Ven, Marion Hendriks, Harry van Dijken, Stefanie Lenz, Martijn Vos, José A. M. Borghans, Debbie van Baarle and Jørgen de Jonge
Vaccines 2024, 12(4), 419; https://doi.org/10.3390/vaccines12040419 - 15 Apr 2024
Viewed by 760
Abstract
To protect older adults against influenza A virus (IAV) infection, innovative strategies are imperative to overcome the decrease in protective immune response with age. One approach involves the boosting of CD8+ T cells at middle age that were previously induced by natural infection. [...] Read more.
To protect older adults against influenza A virus (IAV) infection, innovative strategies are imperative to overcome the decrease in protective immune response with age. One approach involves the boosting of CD8+ T cells at middle age that were previously induced by natural infection. At this stage, the immune system is still fit. Given the high conservation of T-cell epitopes within internal viral proteins, such a response may confer lasting protection against evolving influenza strains at older age, also reducing the high number of influenza immunizations currently required. However, at the time of vaccination, some individuals may have been more recently exposed to IAV than others, which could affect the T-cell response. We therefore investigated the fundamental principle of how the interval between the last infection and booster immunization during middle age influences the CD8+ T-cell response. To model this, female mice were infected at either 6 or 9 months of age and subsequently received a heterosubtypic infection booster at middle age (12 months). Before the booster infection, 6-month-primed mice displayed lower IAV-specific CD8+ T-cell responses in the spleen and lung than 9-month-primed mice. Both groups were better protected against the subsequent heterosubtypic booster infection compared to naïve mice. Notably, despite the different CD8+ T-cell levels between the 6-month- and 9-month-primed mice, we observed comparable responses after booster infection, based on IFNγ responses, and IAV-specific T-cell frequencies and repertoire diversity. Lung-derived CD8+ T cells of 6- and 9-month-primed mice expressed similar levels of tissue-resident memory-T-cell markers 30 days post booster infection. These data suggest that the IAV-specific CD8+ T-cell response after boosting is not influenced by the time post priming. Full article
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11 pages, 259 KiB  
Article
Respiratory Syncytial Vaccination: Parents’ Willingness to Vaccinate Their Children
by Vincenza Sansone, Silvia Angelillo, Francesca Licata, Grazia Miraglia del Giudice and Gabriella Di Giuseppe
Vaccines 2024, 12(4), 418; https://doi.org/10.3390/vaccines12040418 - 15 Apr 2024
Viewed by 773
Abstract
Background: This study was conducted to assess parents’ willingness to vaccinate their children with the RSV vaccine and the key predictors of this intention among parents in Italy. Methods: Data were collected using an anonymous self-administered questionnaire from April to November 2023, targeting [...] Read more.
Background: This study was conducted to assess parents’ willingness to vaccinate their children with the RSV vaccine and the key predictors of this intention among parents in Italy. Methods: Data were collected using an anonymous self-administered questionnaire from April to November 2023, targeting parents in public kindergartens and nursery schools in southern Italy. The survey assessed parents’ socio-demographic characteristics, health-related details, their child’s health status, attitudes toward RSV infection and its vaccine, and their source(s) of information. Results: A total of 404 parents agreed to participate in the study. Only 18.2% of participants were very concerned that their children could get infected by RSV, and this concern was more likely among parents whose child had been diagnosed with bronchiolitis, those who received information from HCWs, those who had heard of RSV, and those who needed additional information. Almost half (51.3%) were willing to vaccinate their child, and this inclination was more likely among fathers, employed parents, those with daughters, those who had heard of RSV, those who received information from HCWs, and those who needed additional information. Conclusions: An educational campaign regarding a future RSV vaccine, especially about its safety and efficacy, is needed in order to improve parents’ willingness. Full article
(This article belongs to the Section Vaccines against Infectious Diseases)
20 pages, 3480 KiB  
Article
Engineered Multivalent Nanobodies Efficiently Neutralize SARS-CoV-2 Omicron Subvariants BA.1, BA.4/5, XBB.1 and BQ.1.1
by Jiali Wang, Bingjie Shi, Hanyi Chen, Mengyuan Yu, Peipei Wang, Zhaohui Qian, Keping Hu and Jianxun Wang
Vaccines 2024, 12(4), 417; https://doi.org/10.3390/vaccines12040417 - 15 Apr 2024
Viewed by 1255
Abstract
Most available neutralizing antibodies are ineffective against highly mutated SARS-CoV-2 Omicron subvariants. Therefore, it is crucial to develop potent and broad-spectrum alternatives to effectively manage Omicron subvariants. Here, we constructed a high-diversity nanobody phage display library and identified nine nanobodies specific to the [...] Read more.
Most available neutralizing antibodies are ineffective against highly mutated SARS-CoV-2 Omicron subvariants. Therefore, it is crucial to develop potent and broad-spectrum alternatives to effectively manage Omicron subvariants. Here, we constructed a high-diversity nanobody phage display library and identified nine nanobodies specific to the SARS-CoV-2 receptor-binding domain (RBD). Five of them exhibited cross-neutralization activity against the SARS-CoV-2 wild-type (WT) strain and the Omicron subvariants BA.1 and BA.4/5, and one nanobody demonstrated marked efficacy even against the Omicron subvariants BQ.1.1 and XBB.1. To enhance the therapeutic potential, we engineered a panel of multivalent nanobodies with increased neutralizing potency and breadth. The most potent multivalent nanobody, B13-B13-B13, cross-neutralized all tested pseudoviruses, with a geometric mean of the 50% inhibitory concentration (GM IC50) value of 20.83 ng/mL. An analysis of the mechanism underlying the enhancement of neutralization breadth by representative multivalent nanobodies demonstrated that the strategic engineering approach of combining two or three nanobodies into a multivalent molecule could improve the affinity between a single nanobody and spike, and could enhance tolerance toward escape mutations such as R346T and N460K. Our engineered multivalent nanobodies may be promising drug candidates for treating and preventing infection with Omicron subvariants and even future variants. Full article
(This article belongs to the Special Issue SARS-CoV-2 Variants: Unraveling Vaccines and Immune Responses)
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12 pages, 1831 KiB  
Article
The Effect of an Attenuated Live Vaccine against Salmonid Rickettsial Septicemia in Atlantic Salmon (Salmo salar) Is Highly Dependent on Water Temperature during Immunization
by Rolf Hetlelid Olsen, Frode Finne-Fridell, Marianne Bordevik, Anja Nygaard, Binoy Rajan and Marius Karlsen
Vaccines 2024, 12(4), 416; https://doi.org/10.3390/vaccines12040416 - 15 Apr 2024
Viewed by 1091
Abstract
Salmonid Rickettsial Septicemia (SRS), caused by the bacterium Piscirickettsia salmonis, is the main reason for antibiotic usage in the Chilean aquaculture industry. In 2016, a live attenuated vaccine (ALPHA JECT LiVac® SRS, PHARMAQ AS) was licensed in Chile and has been [...] Read more.
Salmonid Rickettsial Septicemia (SRS), caused by the bacterium Piscirickettsia salmonis, is the main reason for antibiotic usage in the Chilean aquaculture industry. In 2016, a live attenuated vaccine (ALPHA JECT LiVac® SRS, PHARMAQ AS) was licensed in Chile and has been widely used in farmed salmonids since then. In experimental injection and cohabitation laboratory challenge models, we found that the vaccine is effective in protecting Atlantic salmon (Salmo salar) for at least 15 months against P. salmonis-induced mortality. However, the protection offered by the vaccine is sensitive to temperature during immunization. Fish vaccinated and immunized at 10 °C and above were well protected, but those immunized at 7 °C and 8 °C (the lower end of the temperature range commonly found in Chile) experienced a significant loss of protection. This temperature-dependent loss of effect correlated with the amount of vaccine-strain RNA detected in the liver the first week after vaccination and with in vitro growth curves, which failed to detect any growth at 8 °C. We found that good vaccine efficacy can be restored by exposing fish to 15 °C for the first five days after vaccination before lowering the temperature to 7 °C for the remaining immunization period. This suggests that maintaining the correct temperature during the first few days after vaccination is crucial for achieving a protective immune response with ALPHA JECT LiVac® SRS. Our results emphasize the importance of temperature control when vaccinating poikilothermic animals with live vaccines. Full article
(This article belongs to the Section Attenuated/Inactivated/Live and Vectored Vaccines)
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10 pages, 1232 KiB  
Brief Report
Sex-Dependent Effects on Influenza-Specific Antibody Quantity and Neutralizing Activity following Vaccination of Newborn Non-Human Primates Is Determined by Adjuvants
by Beth C. Holbrook, Elene A. Clemens and Martha A. Alexander-Miller
Vaccines 2024, 12(4), 415; https://doi.org/10.3390/vaccines12040415 - 15 Apr 2024
Viewed by 759
Abstract
A number of studies have demonstrated the role of sex in regulating immune responses to vaccination. However, these findings have been limited to adults for both human and animal models. As a result, our understanding of the impact of sex on vaccine responses [...] Read more.
A number of studies have demonstrated the role of sex in regulating immune responses to vaccination. However, these findings have been limited to adults for both human and animal models. As a result, our understanding of the impact of sex on vaccine responses in the newborn is highly limited. Here, we probe this important question using a newborn non-human primate model. We leveraged our prior analysis of two cohorts of newborns, with one being mother-reared and one nursery-reared. This provided adequate numbers of males and females to interrogate the impact of sex on the response to inactivated influenza vaccines alone or adjuvanted with R848, flagellin, or both. We found that, in contrast to what has been reported in adults, the non-adjuvanted inactivated influenza virus vaccine induced similar levels of virus-specific IgG in male and female newborns. However, the inclusion of R848, either alone or in combination with flagellin, resulted in higher antibody titers in females compared to males. Sex-specific increases in the neutralizing antibody were only observed when both R848 and flagellin were present. These data, generated in the highly translational NHP newborn model, provide novel insights into the role of sex in the immune response of newborns. Full article
(This article belongs to the Section Influenza Virus Vaccines)
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