Vaccines, Volume 11, Issue 10 (October 2023) – 116 articles

The association between vaccines and ocular disorders has attracted significant attention in scientific research. Numerous mainstream vaccines are associated with a range of uveitis types, including anterior, intermediate, and posterior uveitis. Additionally, they are associated with distinct ocular diseases such as multifocal choroiditis, Vogt–Koyanagi–Harada (VKH) disease, acute posterior multifocal placoid pigment epitheliopathy (APMPPE), and multiple evanescent white dot syndrome (MEWDS). These ocular conditions are often transient, with a vast majority of patients experiencing improvement after steroid intervention. To date, numerous cases of vaccine-induced uveitis have been reported. This study analyzed the correlation between antiviral vaccines, including the hepatitis B virus (HBV), human papillomavirus (HPV), measles–mumps–rubella (MMR), varicella zoster virus (VZV), and influenza vaccines, and different manifestations of uveitis. This is the first comprehensive study to offer a detailed analysis of uveitis types induced by antiviral vaccines. Through an extensive database search, we found a particularly strong link between influenza vaccines, followed by VZV and HPV vaccines. While anterior uveitis is common, conditions such as APMPPE, MEWDS, and VKH are particularly notable and merit careful consideration in clinical practice. Corticosteroid treatment was effective; however, half of the observed patients did not achieve full recovery, indicating potentially prolonged effects of the vaccine. Full article

Background: The emergence of the SARS-CoV-2 (COVID-19) pandemic has accelerated work on the creation of effective vaccines, both in terms of previously known vector vaccines and new-generation (mRNA) vaccines. The scientific research on vaccination against COVID-19 infection is limited; therefore, understanding how the immune system responds to vaccines is critical. In our study, we conducted a long-term analysis of the presence and persistence of the immune response via chemiluminescence, analyzing the level of IgG antibodies and neutralizing antibodies in subjects vaccinated with two types of mRNA (Comirnaty) and vector (Vaxzevria) vaccines. Materials and methods: Healthcare workers and a group of teachers were recruited for this study according to the 2021 government-launched vaccination calendar. They received two doses of the Comirnaty or Vaxzevria vaccine. SRBD (spike-receptor binding domain) IgG antibody levels were measured monthly for 6 consecutive months with a chemiluminescent assay (CLIA) and neutralizing antibodies for two periods—1 and 5 months from the completion of the vaccination course. Results: 168 people were recruited for this study: 135 people for the mRNA vaccine group and 33 people for the vector vaccine group. Comparing the serum IgG levels between the two types of vaccines, a significant difference in median values can be noted at all time points. In consecutive months, the mRNA-vaccinated group exhibited significantly higher SRBD levels compared to the vector group, with peak concentrations at one month after the complete vaccination cycle (745 AU/mL vs. 15.44 AU/mL; p < 0.001). Peak antibody concentration for the vector vaccine was observed one month later, at the third follow-up visit; however, the median IgG concentration was almost 7.7 times higher for the Comirnaty group. Both products were effective in stimulating neutralizing antibody production after vaccination. Higher median values were observed for the mRNA vaccines in both evaluations. At first evaluation, the median value for NA concentration in the Comirnaty group was 6 times higher than in the Vaxzevria group (median value 12.23 [IQR 27.3] vs. 1.7 [IQR 3.3]; p < 0.001. Conclusions: People vaccinated with the mRNA vaccine (Comirnaty) showed a stronger immune response to the vaccination than the group of people administered the vector vaccine (Vaxzevria). The Comirnaty group showed higher levels of IgG, including neutralizing antibodies, at all time points during the follow-up period, and this was independent of having had a SARS-CoV-2 infection. A natural decrease in antibody levels was seen within 6 months. A booster vaccination may be required. No serious side effects were observed in either group. Full article

Vaccination against COVID-19 and influenza provides the best defense against morbidity and mortality. Administering both vaccines concurrently may increase vaccination rates and reduce the burden on the healthcare system. This study evaluated the immunogenicity of healthcare workers in Israel who were co-administered with the Omicron BA.4/BA.5 bivalent COVID-19 vaccine and the 2022–2023 quadrivalent influenza vaccine. SARS-CoV-2 neutralizing antibody titers were measured via microneutralization while influenza antibody titers were measured via hemagglutination inhibition. No immunogenic interference was observed by either vaccine when co-administered. Antibody titers against SARS-CoV-2 variants increased significantly in the cohort receiving the COVID-19 vaccine alone and in combination with the influenza vaccine. Antibody titers against the A/H1N1 influenza strain increased significantly in the cohort receiving the influenza vaccine alone and in combination with the COVID-19 vaccine. Antibody titers against B/Victoria increased significantly in the cohort that received both vaccines. This study has important public health implications for the 2023–2024 winter season, and supports co-administration of both vaccines as a viable immunization strategy. Full article

Objective and Participants: The authors sought an updated examination of attitudes toward Human Papillomavirus (HPV) catch-up vaccination among college students at a private religious university. Methods: A total of 1557 college students completed a 62-question survey of religious and HPV vaccination attitudes during the fall of 2021. Students’ willingness to receive catch-up HPV vaccination and willingness to vaccinate a future child against HPV were recorded. Results: Of the 46.8% of students who reported being unvaccinated or unaware of vaccination status, ~26% reported being uninterested in receiving catch-up HPV vaccination; ~22% of all students surveyed reported being unwilling to vaccinate a future child against HPV. The strongest predictors of vaccine hesitancy included religious concerns about sexual abstinence and safety concerns. Conclusions: College health professionals can increase the rate of HPV vaccination among college students and subsequent future generations by addressing the safety and utility of the vaccine regardless of intentions for sexual abstinence prior to marriage. Additionally, rather than a uniform approach to all students who self-identify as Christian, an effort to identify and discuss the unique religiously influenced beliefs of individual students is recommended when discussing HPV vaccination. Full article

A chimeric pestivirus (KD26_E2LOM) was prepared by inserting the E2 gene of the classical swine fever virus (CSFV) LOM strain into the backbone of the bovine viral diarrhea virus (BVDV) KD26 strain. KD26_E2LOM was obtained by transfecting the cDNA pACKD26_E2LOM into PK-15 cells. KD26_E2LOM chimeric pestivirus proliferated to titers of 10^6.5 TCID₅₀/mL and 10^8.0 TCID₅₀/mL at 96 h post-inoculation into PK-15 cells or MDBK cells, respectively. It also reacted with antibodies specific for CSFV E2 and BVDV E^rns, but not with an anti-BVDV E2 antibody. Piglets (55–60 days old) inoculated with a high dose (10^7.0 TCID₅₀/mL) of KD26_E2LOM produced high levels of CSFV E2 antibodies. In addition, no co-habiting pigs were infected with KD26_E2LOM; however, some inoculated pigs excreted the virus, and the virus was detected in some organs. When pregnant sows were inoculated during the first trimester (55–60 days) with a high dose (10^7.0 TCID₅₀/mL) of KD26_E2LOM, anti-CSFV E2 antibodies were produced at high levels; chimeric pestivirus was detected in one fetus and in the ileum of one sow. When 5-day-old calves that did not consume colostrum received a high dose (10^7.0 TCID₅₀/mL) of KD26_E2LOM, one calf secreted the virus in both feces and nasal fluid on Day 2. A high dose of KD26_E2LOM does not induce specific clinical signs in most animals, does not spread from animal to animal, and generates CSFV E2 antibodies with DVIA functions. Therefore, chimeric pestivirus KD26_E2LOM is a potential CSFV live marker vaccine. Full article

Objective: In this Italian population-based study, we aimed to evaluate the neurological complications after the first and/or second dose of COVID-19 vaccines and factors potentially associated with these adverse effects. Methods: Our study included adults aged 18 years and older who received two vaccine doses in the vaccination hub of Novegro (Milan, Lombardy) between 7 and 16 July 2021. The NEURO-COVAX questionnaire was able to capture the neurological events, onset and duration. That data that were digitized centrally by the Lombardy region were used to match the demographic/clinical characteristics and identify a vulnerability profile. Associations between vaccine lines and the development of complications were assessed. Digital healthcare system matching was also performed to evaluate severe neurological complications (Guillain-Barrè syndrome, Bell’s palsy, transverse myelitis, encephalitis) and the incidence of hospital admissions and/or the mortality rate after two doses of the vaccines. Results: The NEURO-COVAX-cohort included 19.108 vaccinated people: 15.368 with BNT162b2, 2077 with mRNA-1273, 1651 with ChAdOx1nCov-19, and 12 with Ad26.COV2.S who were subsequently excluded. Approximately 31.2% of our sample developed post-vaccination neurological complications, particularly with ChAdOx1nCov-19. A vulnerable clinical profile emerged, where over 40% of the symptomatic people showed comorbidities in their clinical histories. Defining the neurological risk profile, we found an increased risk for ChAdOx1nCov-19 of tremors (vs. BNT162b2, OR: 5.12, 95% CI: 3.51–7.48); insomnia (vs. mRNA-1273, OR: 1.87, 95% CI: 1.02–3.39); muscle spasms (vs. BNT162b2, OR: 1.62, 95% CI: 1.08–2.46); and headaches (vs. BNT162b2, OR: 1.49, 95% CI: 0.96–1.57). For mRNA-1273, there were increased risks of parethesia (vs. ChAdOx1nCov-19, OR: 2.37, 95% CI: 1.48–3.79); vertigo (vs. ChAdOx1nCov-19, OR: 1.68, 95% CI: 1.20–2.35); diplopia (vs. ChAdOx1nCov-19, OR: 1.55, 95% CI: 0.67–3.57); and sleepiness (vs. ChAdOx1nCov-19, OR: 1.28, 95% CI: 0.98–1.67). In the period that ranged from March to August 2021, no one was hospitalized and/or died of severe complications related to COVID-19 vaccinations. Discussion: This study estimates the prevalence and risk for neurological complications potentially associated with COVID-19 vaccines, thus improving the vaccination guidelines and loading in future personalized preventive medicine. Full article

(1) Background and Purpose: Ebola virus (EBOV) is the causative agent of Ebola virus disease (EVD), which causes extremely high mortality and widespread epidemics. The only glycoprotein (GP) on the surface of EBOV particles is the key to mediating viral invasion into host cells. DNA vaccines for EBOV are in development, but their effectiveness is unclear. The lack of immune characteristics resides in antigenic MHC class II reactivity. (2) Methods: We selected MHC-II molecules from four human leukocyte antigen II (HLA-II) superfamilies with 98% population coverage and eight mouse H2-I alleles. IEDB, NetMHCIIpan, SYFPEITHI, and Rankpep were used to screen MHC-II-restricted epitopes with high affinity for EBOV GP. Further immunogenicity and conservation analyses were performed using VaxiJen and BLASTp, respectively. EpiDock was used to simulate molecular docking. Cluster analysis and binding affinity analysis of EBOV GP epitopes and selected MHC-II molecules were performed using data from NetMHCIIpan. The selective GP epitopes were verified by the enzyme-linked immunospot (ELISpot) assay using splenocytes of BALB/c (H2d), C3H, and C57 mice after DNA vaccine pVAX-GP_EBO immunization. Subsequently, BALB/c mice were immunized with Protein-GP_EBO, plasmid pVAX-GP_EBO, and pVAX-LAMP/GP_EBO, which encoded EBOV GP. The dominant epitopes of BALB/c (H-2-I-AdEd genotype) mice were verified by the enzyme-linked immunospot (ELISpot) assay. It is also used to evaluate and explore the advantages of pVAX-LAMP/GP_EBO and the reasons behind them. (3) Results: Thirty-one HLA-II-restricted and 68 H2-I-restricted selective epitopes were confirmed to have high affinity, immunogenicity, and conservation. Nineteen selective epitopes have cross-species reactivity with good performance in MHC-II molecular docking. The ELISpot results showed that pVAX-GP_EBO could induce a cellular immune response to the synthesized selective peptides. The better immunoprotection of the DNA vaccines pVAX-LAMP/GP_EBO coincides with the enhancement of the MHC class II response. (4) Conclusions: Promising MHC-II-restricted candidate epitopes of EBOV GP were identified in humans and mice, which is of great significance for the development and evaluation of Ebola vaccines. Full article

The aim of this study was to assess the organisational process of vaccination within the National Vaccination Programme against COVID-19 (NVP) in the professional group of teachers in Pomeranian Province, Poland. The main goal of the survey was to assess the quality of planning and executing of the NVP and to find a correlation between social and employment placements with the level of perception of chosen quality indicators of the NVP. The presented cross-sectional survey was conducted among 4622 teachers from all levels of education in public and non-public institutions who received the SARS-CoV-2 virus vaccination campaign with the vaccine from AstraZeneca as part of the NVP. The survey was conducted using an original, self-designed questionnaire prepared for this study and distributed to teachers in the form of an online survey via email. Bayesian logistic and linear regression were used to estimate the relationship between predictors and dependent variables. Age was the main factor associated with the performance assessment of the vaccination centre (log[BF] = 0.86–16.88), while gender was the main factor associated with the assessment of NVP (log[BF] = 3.15–10,6). The evaluation of the vaccination registration process (log[BF] = −7.01–50.26) and the evaluation of the information received on the management of post-vaccination reactions (log[BF] = −2.22–65.26) were significant parts of the NVP. It is crucial to tailor information messages to the age and gender of the recipients and to ensure the quality of the information provided by medical personnel, in particular the possible occurrence of vaccination reactions and how to deal with them. Full article

The vaccination of children against human papillomavirus (HPV) effectively prevents HPV infection and HPV-related cancers in women and men. However, HPV vaccination programs are met with vaccine hesitancy, which varies between countries. The coverage in Poland is low, although introducing nationally funded HPV vaccination for girls aged 12–13 in mid-2023 may increase it. The uptake of the HPV vaccine in adolescents is highly affected by parental decisions, which in turn can be influenced by interactions with the physician. The present representative study aimed to analyze the acceptance of the HPV vaccine among Polish parents (n = 360) and the level of trust in HPV vaccination in the pediatrician/general practitioner who takes care of their children aged 9–15 years. The data were gathered in September 2022 using computer-assisted telephone interviews. Most surveyed parents reported trusting their child’s physician regarding vaccine recommendations (89.2%) and vaccinated their child with all or most of the vaccines recommended by a national vaccination guideline (94.7%). However, 13.3% declared themselves as moderate or strong vaccine opponents, a group characterized by high (83.4%) distrust in physicians. There was no difference in the awareness of HPV in groups varying in trusting the physicians, but parents who trusted them were more frequently aware of the HPV vaccine. Parental willingness to vaccinate their child against HPV was highly differentiated by the level of trust in the child’s physician. The results highlight that trust in physicians is a critical factor shaping decisions for children’s vaccination, stressing a continuous need to improve strategies to communicate with patients. Full article

Alongside the development and progress in cancer immunotherapy, research in oncolytic viruses (OVs) continues advancing novel treatment strategies to the clinic. With almost 50 clinical trials carried out over the last decade, the opportunities for intervention using OVs are expanding beyond the old-fashioned concept of “lytic killers”, with promising breakthrough therapeutic strategies focused on leveraging the immunostimulatory potential of different viral platforms. This review presents an overview of non-human-adapted RNA viruses engineered for cancer therapy. Moreover, we describe the diverse strategies employed to manipulate the genomes of these viruses to optimize their therapeutic capabilities. By focusing on different aspects of this particular group of viruses, we describe the insights into the promising advancements in the field of virotherapy and its potential to revolutionize cancer treatment. Full article

The COVID-19 pandemic posed challenges to communicating accurate information about vaccines because of the spread of misinformation. The European Medicines Agency (EMA) tried to reassure the public by communicating early on about the development and approval of COVID-19 vaccines. The EMA surveyed patients/consumers, healthcare professional organizations, and individual stakeholders, both at the EU level and in an Italian regional context. The objectives of the study were to see if the EMA’s core information materials were informative and well-understood and which communication channels were preferred by the public. The main findings showed that individual patients/consumers generally prefer to obtain information about COVID-19 vaccines from the internet or mass media, while organizations and individual healthcare professionals prefer to obtain information from national and international health authorities. Both at EU and local levels, participants had a good understanding of the key messages from regulators and found the materials useful and relevant. However, some improvements were recommended to the visual, text, and dissemination formats, including publishing more information on safety and using a more public-friendly language. Also, it was recommended to maintain the EMA’s approach of using media, stakeholder engagement, and web-based formats to communicate about COVID-19 vaccines. In conclusion, user-testing of proactive communication materials aimed to prebunk misinformation during a public health crisis helps to ensure that users understand the development and safety of novel vaccine technologies. This information can then be used as a basis for further evidence-based communication activities by regulators and public health bodies in an emergency context. Full article

This study aimed at identifying factors influencing SARS-CoV-2-specific IgG antibody levels after vaccination and/or infection. Between January 2022 and March 2023, 2000 adults (≥18 years, Salzburg, Austria) participated in this population-based seroprevalence study by providing 3 mL of blood to detect SARS-CoV-2-specific IgG antibodies using an anti-SARS-CoV-2 IgG quantitative assay and by completing a self-designed questionnaire including anthropometric factors, vaccination information, and medical history. For 77 of the participants, a time-course study up to 24 weeks post vaccination or quarantine end was performed. Convalescent-only subjects had the lowest median antibody titer (65.6 BAU/mL) compared to vaccinated and hybrid immunized subjects (p-value < 0.0001) The type of vaccine as well as vaccine combinations significantly influenced the levels of SARS-CoV-2 spike-protein-specific IgG, ranging from a median antibody level of 770.5 BAU/mL in subjects who were vaccinated only to 3020.0 BAU/mL in hybrid immunized subjects (p-value < 0.0001). Over time, a significant decline in the levels of neutralizing antibodies was found. Depending on the subpopulation analyzed, further significant influencing factors included sex assigned at birth, disease severity, chronic diseases, and medication. A hybrid immunization resulted in more robust immune responses. Nevertheless, there were multiple other factors impacting these responses. This knowledge should be included in future vaccination strategies and serve as a guide in the development of personalized medicine. Full article

To understand the HPV infection profiles among Chinese HIV/AIDS patients and the HPV vaccine acceptance among unvaccinated Chinese people with different HIV infection statuses after the HPV vaccine launch in China, this study searched Web of Science, PubMed, Cochrane Library, Embase, Scopus, CNKI, WANFANG, SinoMed, and VIP databases up to 23 June 2023, according to the registered protocol (CRD42023449913). A total of 58 studies were included. The results showed that the HPV infection rate among Chinese HIV/AIDS patients was 52.54% (95% CI: 42.11–62.86%) and higher in males than in females (74.55% vs. 41.04%); meanwhile, the rate was higher in the anus than in the cervix (69.22% vs. 41.71%). Although there was no statistical difference, the high-risk HPV infection rate (38.98%) was higher than low-risk HPV (23.86%), and single infections were more common (28.84%) than multiple infections (19.23%). HPV vaccine acceptance among the unvaccinated Chinese population was 59.19% (95% CI: 52.50–65.89%), and was slightly higher among HIV-infected rather than non-HIV-infected individuals (67.72% vs. 59.58%). There was a difference in acceptance among respondents from different regions. Although the difference in acceptance rate between males and females was not statistically significant (61.10% vs. 61.18%), MSM had a higher acceptance rate than non-MSM (84.28% vs. 59.05%). HPV infection is prevalent among HIV patients, demonstrating the need to increase the frequency of HPV screening for PLWH. The HPV vaccine acceptance rate is higher than that of non-HIV-infected individuals. Male acceptance is almost the same as female’s, with MSM acceptance higher than non-MSM, suggesting that using MSM, especially MSM in PLWH, as an entry point may be a practical avenue to explore to further expand the scope of HPV vaccination. Full article

Assessing immune responses post-SARS-CoV-2 vaccination is crucial for optimizing vaccine strategies. This prospective study aims to evaluate immune responses and breakthrough infection in 235 infection-naïve healthcare workers up to 13–15 months after initial vaccination in two vaccine groups (108 BNT/BNT/BNT and 127 ChAd/ChAd/BNT). Immune responses were assessed using the interferon-gamma enzyme-linked immunospot (ELISPOT) assay, total immunoglobulin, and neutralizing activity through surrogate virus neutralization test at nine different time points. Both groups exhibited peak responses one to two months after the second or third dose, followed by gradual declines over six months. Notably, the ChAd group exhibited a gradual increase in ELISPOT results, but their antibody levels declined more rapidly after reaching peak response compared to the BNT group. Six months after the third dose, both groups had substantial cellular responses, with superior humoral responses in the BNT group (p < 0.05). As many as 55 breakthrough infection participants displayed higher neutralization activities against Omicron variants, but similar cellular responses compared to 127 infection-naïve individuals, suggesting cross-immunity. Distinct neutralization classifications (<30%, >80% inhibition) correlated with different ELISPOT results. Our study reveals diverse immune response patterns based on vaccine strategies and breakthrough infections, emphasizing the importance of understanding these dynamics for optimized vaccination decisions. Full article

Immune dysregulation and cancer treatment may affect SARS-CoV-2 vaccination protection. Antibody production by B-cells play a vital role in the control and clearance of the SARS-CoV-2 virus. This study prospectively explores B-cell seroconversion following SARS-CoV-2 immunization in healthy individuals and non-small cell lung cancer (NSCLC) patients undergoing oncological treatment. 92 NSCLC patients and 27 healthy individuals’ blood samples were collected after receiving any COVID-19 vaccine. Serum and mononuclear cells were isolated, and a serum surrogate virus neutralization test kit evaluated SARS-CoV-2 antibodies. B-cell subpopulations on mononuclear cells were characterized by flow cytometry. Patients were compared based on vaccination specifications and target mutation oncological treatment. A higher percentage of healthy individuals developed more SARS-CoV-2 neutralizing antibodies than NSCLC patients (63% vs. 54.3%; p = 0.03). NSCLC patients receiving chemotherapy (CTX) or tyrosine kinase inhibitors (TKIs) developed antibodies in 45.2% and 53.7%, of cases, respectively, showing an impaired antibody generation. CTX patients exhibited trends towards lower median antibody production than TKIs (1.0, IQR 83 vs. 38.23, IQR 89.22; p = 0.069). Patients receiving immunotherapy did not generate antibodies. A sub-analysis revealed that those with ALK mutations exhibited non-significant trends towards higher antibody titers (63.02, IQR 76.58 vs. 21.78, IQR 93.5; p = 0.1742) and B-cells quantification (10.80, IQR 7.52 vs. 7.22, IQR 3.32; p = 0.1382) against the SARS-CoV-2 spike protein than EGFR patients; nonetheless, these differences were not statistically significant. This study shows that antibodies against SARS-CoV-2 may be impaired in patients with NSCLC secondary to EGFR-targeted TKIs compared to ALK-directed treatment. Full article

Prevention of infections is crucial in solid organ transplant (SOT) candidates and recipients. These patients are exposed to an increased infectious risk due to previous organ insufficiency and to pharmacologic immunosuppression. Besides infectious-related morbidity and mortality, this vulnerable group of patients is also exposed to the risk of acute decompensation and organ rejection or failure in the pre- and post-transplant period, respectively, since antimicrobial treatments are less effective than in the immunocompetent patients. Vaccination represents a major preventive measure against specific infectious risks in this population but as responses to vaccines are reduced, especially in the early post-transplant period or after treatment for rejection, an optimal vaccination status should be obtained prior to transplantation whenever possible. This review reports the currently available data on the indications and protocols of vaccination in SOT adult candidates and recipients. Full article

Background. The risk of herpes zoster reactivation is increased in immunocompromised patients, especially in those with immune-mediated inflammatory diseases (IMIDs) on Janus kinase inhibitor (JAKi) treatment. The recombinant subunit herpes zoster vaccine (RZV) is a non-live vaccine, recently approved for this subgroup of patients, which shows high rates of vaccine effectiveness, with few adverse effects reported in clinical trials. Purpose. The aim of this real-world study was to determine the immunogenicity and safety of RZV in IMID patients on JAKi treatment. Methods. The increase in the concentration of anti-gE antibody for varicella zoster virus post-vaccination, compared to the pre-vaccination concentration, was analyzed to test the humoral immune response. Adverse effects after the first and second vaccine doses were registered. Results. In total, 49 patients were analyzed, and a fourfold increase in antibody concentration was achieved in almost 40% of subjects, with only one serious local adverse effect. Discussion. The resulting immunogenicity was lower than that observed in clinical trials, probably due to the presence of immune disease and immunosuppressive treatment, and to the fact that this was a real-world study. No differences in response according to age, previous virus zoster reactivation, or concomitant treatments were found. Conclusions. RZV was well tolerated and reached the immune response objective in 40% of patients. These results reinforce the importance of including RZV vaccination for immunosuppressed patients. Real-world studies regarding vaccine effectiveness are still needed in order to gain a full understanding of the response to RZV in this group of patients. Full article

Vaccine immunogenicity still represents an unmet need in specific populations, such as people from developing countries and “edge populations”. Both intrinsic and extrinsic factors, such as the environment, age, and dietary habits, influence cellular and humoral immune responses. The human microbiota represents a potential key to understanding how these factors impact the immune response to vaccination, with its modulation being a potential step to address vaccine immunogenicity. The aim of this narrative review is to explore the intricate interactions between the microbiota and the immune system in response to vaccines, highlighting the state of the art in gut microbiota modulation as a novel therapeutic approach to enhancing vaccine immunogenicity and laying the foundation for future, more solid data for its translation to the clinical practice. Full article

Pregnant women are considered to be a population vulnerable to influenza and COVID-19 infections, and the latest guidelines consistently recommend that they receive influenza and COVID-19 vaccinations. A cross-sectional questionnaire-based study was conducted among pregnant women in Poland to determine which factors have the greatest impact on their decision to vaccinate against influenza and COVID-19. A total of 515 pregnant women participated in the study. Among them, 38.4% (n = 198) demonstrated a positive attitude toward influenza vaccination, and 64.3% (n = 331) demonstrated a positive attitude toward COVID-19 vaccination. Logistic regression analysis revealed that the strongest influence on positive attitudes toward COVID-19 vaccination is having it recommended by an obstetrician–gynecologist (OR = 2.439, p = 0.025). The obstetrician–gynecologist’s recommendation to vaccinate against influenza also significantly influences the decision to vaccinate (OR = 5.323). The study results also show a strong correlation between the obstetrician–gynecologist as a source of information on influenza and vaccination and participants’ positive attitudes toward vaccination (OR = 4.163). Obstetricians have a significant influence on pregnant women’s decisions regarding vaccinations. Further recommendations to vaccinate and awareness-raising among obstetricians may be needed to increase the vaccination rate of pregnant women in Poland. Full article

Cell-based seasonal influenza vaccine viruses may more closely match recommended vaccine strains than egg-based options. We sought to evaluate the effectiveness of seasonal cell-based quadrivalent influenza vaccine (QIVc), as reported in the published literature. A systematic literature review was conducted (PROSPERO CRD42020160851) to identify publications reporting on the effectiveness of QIVc in persons aged ≥6 months relative to no vaccination or to standard-dose, egg-based quadrivalent or trivalent influenza vaccines (QIVe/TIVe). Publications from between 1 January 2016 and 25 February 2022 were considered. The review identified 18 relevant publications spanning three influenza seasons from the 2017–2020 period, with an overall pooled relative vaccine effectiveness (rVE) of 8.4% (95% CI, 6.5–10.2%) for QIVc vs. QIVe/TIVe. Among persons aged 4–64 years, the pooled rVE was 16.2% (95% CI, 7.6–24.8%) for 2017–2018, 6.1% (4.9–7.3%) for 2018–2019, and 10.1% (6.3–14.0%) for 2019–2020. For adults aged ≥65 years, the pooled rVE was 9.9% (95% CI, 6.9–12.9%) in the egg-adapted 2017–2018 season, whereas there was no significant difference in 2018–2019. For persons aged 4–64 years, QIVc was consistently more effective than QIVe/TIVe over the three influenza seasons. For persons aged ≥65 years, protection with QIVc was greater than QIVe or TIVe during the 2017–2018 season and comparable in 2018–2019. Full article

Ribonucleic acid (RNA) viruses pose heavy burdens on public-health systems. Synthetic biology holds great potential for artificially controlling their replication, a strategy that could be used to attenuate infectious viruses but is still in the exploratory stage. Herein, we used the genetic-code expansion technique to convert Enterovirus 71 (EV71), a prototypical RNA virus, into a controllable EV71 strain carrying the unnatural amino acid (UAA) Nε-2-azidoethyloxycarbonyl-L-lysine (NAEK), which we termed an EV71-NAEK virus. After NAEK supplementation, EV71-NAEK could recapitulate an authentic NAEK time- and dose-dependent infection in vitro, which could serve as a novel method to manipulate virulent viruses in conventional laboratories. We further validated the prophylactic effect of EV71-NAEK in two mouse models. In susceptible parent mice, vaccination with EV71-NAEK elicited a strong immune response and protected their neonatal offspring from lethal challenges similar to that of commercial vaccines. Meanwhile, in transgenic mice harboring a PylRS-${\mathrm{tRNA}}_{\mathrm{CUA}}^{\mathrm{Pyl}}$ pair, substantial elements of genetic-code expansion technology, EV71-NAEK evoked an adjustable neutralizing-antibody response in a strictly external NAEK dose-dependent manner. These findings suggested that EV71-NAEK could be the basis of a feasible immunization program for populations with different levels of immunity. Moreover, we expanded the strategy to generate controllable coxsackieviruses for conceptual verification. In combination, these results could underlie a competent strategy for attenuating viruses and priming the immune system via artificial control, which might be a promising direction for the development of amenable vaccine candidates and be broadly applied to other RNA viruses. Full article

Two respiratory syncytial virus (RSV) vaccines (AREXVY^® and ABRYSVO^®) were recently approved for older adults in the US. This study aimed to evaluate the cost-effectiveness of AREXVY^® and ABRYSVO^® from the Hong Kong public healthcare provider’s perspective. A two-year decision-analytical model was developed to examine the outcomes of a single RSV vaccination (AREXVY^® or ABRYSVO^®) compared to no vaccination. Primary outcomes included RSV-related health outcomes, direct medical costs, quality-adjusted life-year (QALY) loss, and incremental cost per QALY (ICER). RSV vaccines are not yet marketed in Hong Kong, base-case analysis, therefore, benchmarked US RSV vaccine prices at 4 levels (25%, 50%, 75%, 100%). AREXVY^® and ABRYSVO^® (versus no vaccination) gained 0.000568 QALY and 0.000647 QALY, respectively. ICERs of ABRYSVO^® (26,209 USD/QALY) and AREXVY^® (47,485 USD/QALY) were lower than the willingness-to-pay threshold (49,594 USD/QALY) at 25% US vaccine price. The RSV attack rate was a common influential factor at all vaccine price levels. The probabilities of AREXVY^® and ABRYSVO^® to be most cost-effective were 0.10% and 97.68%, respectively, at 25% US vaccine price. Single vaccination of ABRYSVO^® or AREXVY^® for older adults appears to gain QALYs over 2 years in Hong Kong. The cost-effectiveness of AREXVY^® and ABRYSVO^® is subject to vaccine price and RSV attack rate. Full article

Intravenously (IV) delivered BCG provides superior tuberculosis (TB) protection compared with the intradermal (ID) route in non-human primates (NHPs). We examined how γδ T cell responses changed in vivo after IV BCG vaccination of NHPs, and whether these correlated with protection against aerosol M. tuberculosis challenge. In the circulation, Vδ2 T cell populations expanded after IV BCG vaccination, from a median of 1.5% (range: 0.8–2.3) of the CD3+ population at baseline, to 5.3% (range: 1.4–29.5) 4 weeks after M. tb, and were associated with TB protection. This protection was related to effector and central memory profiles; homing markers; and production of IFN-γ, TNF-α and granulysin. In comparison, Vδ2 cells did not expand after ID BCG, but underwent phenotypic and functional changes. When Vδ2 responses in bronchoalveolar lavage (BAL) samples were compared between routes, IV BCG vaccination resulted in highly functional mucosal Vδ2 cells, whereas ID BCG did not. We sought to explore whether an aerosol BCG boost following ID BCG vaccination could induce a γδ profile comparable to that induced with IV BCG. We found evidence that the aerosol BCG boost induced significant changes in the Vδ2 phenotype and function in cells isolated from the BAL. These results indicate that Vδ2 population frequency, activation and function are characteristic features of responses induced with IV BCG, and the translation of responses from the circulation to the site of infection could be a limiting factor in the response induced following ID BCG. An aerosol boost was able to localise activated Vδ2 populations at the mucosal surfaces of the lung. This vaccine strategy warrants further investigation to boost the waning human ID BCG response. Full article

Vibrio anguillarum (V. anguillarum) is a bacterium that seriously harms flounder and other aquaculture species. Vaccination is an effective means of preventing vibriosis and is mainly administered by intraperitoneal injection. Effective antigen processing at the initial stage of immunization is essential to elicit adaptive immune responses and improve vaccine efficacy. To understand the early immune response of flounder caused by inactivated V. anguillarum, we detected the transcriptome profiles of the cells in the peritoneal cavity (PoPerCs) after inactivated V. anguillarum immunization. More than 10 billion high-quality reads were obtained, of which about 89.33% were successfully mapped to the reference genome of flounder. A total of 1985, 3072, 4001, and 5476 differentially expressed genes were captured at 6, 12, 24, and 48 h post immunization, respectively. The hub module correlated with the immunization time was identified by WGCNA. GO and KEGG analysis showed that hub module genes were abundantly expressed in various immune-related aspects, including the response to stimuli, the immune system process, signal transducer activity, autophagy, the NOD-like receptor signaling pathway, the toll-like receptor signaling pathway, the T cell receptor signaling pathway, and Th17 cell differentiation. Additionally, genes related to Th cell differentiation are presented as heatmaps. These genes constitute a complex immune regulatory network, mainly involved in pathogen recognition, antigen processing and presentation, and Th cell differentiation. The results of this study provide the first transcriptome profile of PoPerCs associated with inactivated V. anguillarum immunity and lay a solid foundation for further studies on effective V. anguillarum vaccines. Full article

SARS-CoV-2 spike protein is an essential component of numerous protein-based vaccines for COVID-19. The receptor-binding domain of this spike protein is a promising antigen with ease of expression in microbial hosts and scalability at comparatively low production costs. This study describes the production, purification, and characterization of RBD of SARS-CoV-2 protein, which is currently in clinical trials, from a commercialization perspective. The protein was expressed in Pichia pastoris in a large-scale bioreactor of 1200 L capacity. Protein capture and purification are conducted through mixed-mode chromatography followed by hydrophobic interaction chromatography. This two-step purification process produced RBD with an overall productivity of ~21 mg/L at >99% purity. The protein’s primary, secondary, and tertiary structures were also verified using LCMS-based peptide mapping, circular dichroism, and fluorescence spectroscopy, respectively. The glycoprotein was further characterized for quality attributes such as glycosylation, molecular weight, purity, di-sulfide bonding, etc. Through structural analysis, it was confirmed that the product maintained a consistent quality across different batches during the large-scale production process. The binding capacity of RBD of spike protein was also assessed using human angiotensin-converting enzyme 2 receptor. A low binding constant range of KD values, ranging between 3.63 × 10⁻⁸ to 6.67 × 10⁻⁸, demonstrated a high affinity for the ACE2 receptor, revealing this protein as a promising candidate to prevent the entry of COVID-19 virus. Full article

Evidence from countries that achieved a high seasonal influenza vaccination (SIV) coverage suggests that reminders to get vaccinated may increase SIV uptake. The goal of this study was to explore the experience and attitudes of Italian adults toward an active invitation to receive SIV, triggered by different sources and delivered via different communication channels, and to assess the projected benefits of this strategy. A cross-sectional survey on a representative sample of Italian adults was conducted by using computer-assisted web interviewing. Responses from 2513 subjects were analyzed. A total of 52.2% of individuals previously received invitations to undergo SIV and compared with people who did not receive any reminder were three times more likely (68.2% vs. 22.2%) to be vaccinated in the last season. Compared with other sources, reminders sent by general practitioners (GPs) were perceived as the most attractive. As for communication channels, most participants preferred text/instant messaging (24.6%) or email (27.2%), suggesting an acceleration in the Italian digital transformation triggered by the COVID-19 pandemic. Conversely, traditional postal letters or phone calls were preferred by only 17.0% and 8.6% of respondents, respectively. Reminders sent by GPs via text/instant messages or email are a valuable option for increasing SIV uptake among Italian adults. Full article

mRNA was discovered in 1961, but it was not used as a vaccine until after three decades. Recently, the development of mRNA vaccine technology gained great impetus from the pursuit of vaccines against COVID-19. To improve the properties of RNA vaccines, and primarily their circulation time, self-amplifying mRNA and trans-amplifying mRNA were developed. A separate branch of mRNA technology is circular RNA vaccines, which were developed with the discovery of the possibility of translation on their protein matrix. Circular RNA has several advantages over mRNA vaccines and is considered a fairly promising platform, as is trans-amplifying mRNA. This review presents an overview of the mRNA platform and a critical discussion of the more modern self-amplifying mRNA, trans-amplifying mRNA, and circular RNA platforms created on its basis. Finally, the main features, advantages, and disadvantages of each of the presented mRNA platforms are discussed. This discussion will facilitate the decision-making process in selecting the most appropriate platform for creating RNA vaccines against cancer or viral diseases. Full article

Cancer is a leading cause of death worldwide, accounting for millions of deaths every year. Immunotherapy is a groundbreaking approach for treating cancer through harnessing the power of the immune system to target and eliminate cancer cells. Cancer vaccines, one immunotherapy approach, have shown promise in preclinical settings, but researchers have struggled to reproduce these results in clinical settings. However, with the maturity of mRNA technology and its success in tackling the recent coronavirus disease 2019 (COVID-19) pandemic, cancer vaccines are expected to regain attention. In this review, we focused on the recent progress made in mRNA-based cancer vaccines over the past five years. The mechanism of action of mRNA vaccines, advancements in neoantigen discovery, adjuvant identification, and delivery materials are summarized and reviewed. In addition, we also provide a detailed overview of current clinical trials involving mRNA cancer vaccines. Lastly, we offer an insight into future considerations for the application of mRNA vaccines in cancer immunotherapy. This review will help researchers to understand the advances in mRNA-based cancer vaccines and explore new dimensions for potential immunotherapy approaches. Full article

This study addresses the crucial aspect of childhood COVID-19 vaccination and its impact on parental decisions concerning learning modalities during the pandemic. This study aimed to gauge parental hesitancy towards vaccinating their children and its influence on choosing between distance and face-to-face learning options. Following STROBE guidelines for cross-sectional studies, this study surveyed 1973 parents in the United Arab Emirates using Google Forms during the COVID-19 pandemic. The results revealed that while more than half of the parents (51.6%) were willing to vaccinate their children if the COVID-19 vaccine was accessible and affordable, a significant majority (91.2%) expressed concerns about the rapid vaccine development process, which was the primary reason for vaccine rejection. Interestingly, a sizable portion (55.3%) had experienced online learning in the previous academic term, and, of those, 59.6% believed it negatively influenced their children’s academic performance. Consequently, 66.4% expressed intent to shift their children back to face-to-face learning once feasible. Significantly, parents with medical backgrounds were more inclined (91.6%) to opt for face-to-face schooling compared to those without such backgrounds. Logistic regression analysis indicated associations between sociodemographic characteristics, educational level and background, and the decision to return children to face-to-face learning. Interestingly, when it comes to vaccine hesitancy, a noteworthy connection exists between the parents’ reluctance to vaccinate their children and their preference for distance learning. In fact, parents who responded negatively to vaccinating their children against COVID-19, if the vaccine was available, showed a clear preference for the distance learning modality (p-value < 0.0001). This study underscores the complex interplay of factors and community perspectives shaping parental acceptance of childhood COVID-19 vaccination. The development pace of vaccines significantly influences parents’ attitudes and beliefs about vaccination programs. Parents’ medical backgrounds exhibit a clear correlation with their perceptions of sending children back to school safely. This highlights the potential impact of parental medical knowledge on decision making, emphasizing the need to consider parents’ professional backgrounds when devising education- and vaccination-related policies. Full article

This study investigates and compares the predictors of COVID-19 and influenza vaccination confidence and uptake in the U.S. Vaccine hesitancy is defined as the reluctance or refusal (i.e., less than 100% behavioral intention) to vaccinate despite the availability of effective and safe vaccines. Vaccine hesitancy is a major obstacle in the fight against infectious diseases such as COVID-19 and influenza. Predictors of vaccination intention are identified using the reasoned action approach and the integrated behavioral model. Data from two national samples (N = 1131 for COVID-19 and N = 1126 for influenza) were collected from U.S. Qualtrics panels. Tobit regression models were estimated to predict percentage increases in vaccination intention (i.e., confidence) and the probability of vaccination uptake (i.e., intention reaching 100%). The results provided evidence for the reasoned approach and the IBM model and showed that the predictors followed different patterns for COVID-19 and influenza. The implications for intervention strategies and message designs were discussed. Full article