Vaccines最新文献

{"title":"Enhanced Th1 Cellular Immunity Induced by an RSV-F mRNA Vaccine Rationally Designed Using NLP Algorithms.","authors":"Zhi-Wu Xia, Qi Tang, Jun-Jie Pan, Jing Liu, Lan-Xin Jia, Guo-Mei Zhang, Man-Ni Xie, Jia-Hao Zheng, Chuan-Shuo Lv, Lei Zhang, Yan-Hong Shi, Liang He, Min Luo, Jun-Long Zhao","doi":"10.3390/vaccines14040356","DOIUrl":"https://doi.org/10.3390/vaccines14040356","url":null,"abstract":"<p><p><b>Background:</b> Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infections in infants, seniors, and immunocompromised individuals, contributing substantially to the global disease burden. Given the limited preventive options available, developing an effective and safe vaccine remains a public health priority. <b>Methods:</b> An mRNA vaccine encoding the RSV PreF protein was designed and prepared. Antigen properties were evaluated in silico, and the coding sequence was optimized using NLP algorithms. The stability and translational efficiency of the mRNA constructs were verified through in vitro and in vivo assays, followed by immunogenicity evaluation of the formulated mRNA vaccines in a BALB/c mouse model. <b>Results:</b> The optimized mRNA showed predicted improvements in structural stability and a lower free energy state, which were associated with increased translational efficacy in vitro. Correct antigen conformation and retention of key epitopes were confirmed by intracellular staining followed by flow cytometry. A balanced Th1-biased immune response was induced in mice, characterized by high levels of neutralizing antibodies and antigen-specific T-cell immunity, along with enhanced memory T-cell proliferation and differentiation, indicating long-term immunological memory. <b>Conclusions:</b> A novel RSV PreF mRNA vaccine was successfully developed via optimization of protein structure and mRNA sequence. Superior immunogenicity was demonstrated in the BALB/c mouse model, together with promising potential in terms of vaccine safety and immunological persistence. These findings represent a promising step forward in the pursuit of an effective RSV vaccine and suggest the potential of the developed mRNA vaccine to induce substantial immune responses that may correlate with protection in future challenge studies.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vaccination Attitudes in the Adult Population of Kazakhstan: A Nationally Representative Cross-Sectional Study.","authors":"Yerlan Ismoldayev, Anel Ibrayeva, Asset Izdenov, Sergey Lee, Altynay Sadykova, Bolat Sadykov, Shynar Tanabayeva, Ildar Fakhradiyev","doi":"10.3390/vaccines14040353","DOIUrl":"https://doi.org/10.3390/vaccines14040353","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background/Objectives:&lt;/b&gt; Vaccine hesitancy remains a significant public health challenge worldwide, yet nationally representative data from Central Asia are scarce. Evidence on the multidimensional structure of vaccination attitudes and their social patterning in Kazakhstan is limited. The study aimed to assess the distribution of anti-vaccination attitudes among adults in Kazakhstan and to examine their associations with socio-demographic, behavioural, clinical, and territorial characteristics. &lt;b&gt;Methods:&lt;/b&gt; We conducted a cross-sectional, nationally representative survey of adults aged 18-69 years across all 17 regions of Kazakhstan between May and October 2025 (n = 6712). A multistage, stratified cluster sampling design was applied, and analyses incorporated sampling weights and design-based corrections. Vaccination attitudes were measured using the 12-item Vaccination Attitudes Examination (VAX) scale, comprising four subscales: mistrust of vaccine benefit, worries about unforeseen future effects, concerns about commercial profiteering, and preference for natural immunity. Internal consistency and confirmatory factor analysis were performed. Design-adjusted linear regression models were used to identify factors independently associated with each subscale and the overall VAX score. &lt;b&gt;Results:&lt;/b&gt; The weighted mean overall VAX score was 3.70 (95% CI 3.67-3.73) on a 1-6 scale. The highest scores were observed for worries about unforeseen future effects (4.12; 95% CI 4.10-4.14), followed by preference for natural immunity (3.93; 95% CI 3.87-3.98), concerns about commercial profiteering (3.49; 95% CI 3.45-3.52), and mistrust of vaccine benefit (3.27; 95% CI 3.23-3.31). Internal consistency was high for the overall scale (Cronbach's α = 0.861), and the four-factor structure demonstrated acceptable fit (CFI = 0.965; TLI = 0.952; RMSEA = 0.071). In multivariable design-adjusted models, age showed a generally consistent gradient, with lower scores in younger groups and the clearest differences observed among the youngest respondents. Married/cohabiting respondents had lower adjusted scores than single respondents across all subscales and for the overall VAX score. Men had lower adjusted worries scores than women, but sex was not independently associated with the overall VAX score. Diabetes was associated with higher adjusted mistrust, concerns about commercial profiteering, and overall VAX score, but not with worries or preference for natural immunity. Territorial differences were domain-specific: urban residence was associated with lower mistrust and higher worries, while macro-region was significant at the factor level only for worries. &lt;b&gt;Conclusions:&lt;/b&gt; Anti-vaccination attitudes in Kazakhstan exhibit a multidimensional structure and clear socio-demographic patterning. Concerns about long-term safety were the most prominent attitudinal domain, whereas mistrust of vaccine benefit was comparatively less pronounced. Territorial differe","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoimmune Features of Post-COVID-19 Vaccination Syndrome and Their Impacts on the Renin-Angiotensin System.","authors":"Paolo Bellavite, Giuseppe Di Fede, Mauro Mantovani, Elisabetta Zanolin","doi":"10.3390/vaccines14040354","DOIUrl":"https://doi.org/10.3390/vaccines14040354","url":null,"abstract":"<p><p>One of the most critical aspects of post-acute COVID-19 syndrome (PACS) and post-acute COVID-19 vaccination syndrome (PACVS) is the presence of autoantibodies. These autoantibodies are directed against various receptors in the autonomic and cardiovascular systems, including those targeting proteins of the renin-angiotensin system (RAS). The RAS plays a central role in regulating vascular homeostasis, inflammation, and endothelial function. During SARS-CoV-2 infection, the interaction of the spike (S) protein with angiotensin-converting enzyme 2 (ACE2) can alter the balance of the RAS, favoring an imbalance towards the ACE/Angiotensin II/AT1R axis, known for its pro-inflammatory, pro-thrombotic, and vasoconstrictive properties. Similar pathological mechanisms also come into play in response to vaccinations that use the S protein as an antigen. Studies conducted by other groups and us on patients with PACS and PACVS have revealed the presence of autoantibodies directed against these RAS components and the mechanisms by which these antibodies can worsen the clinical situation. In particular, anti-ACE2, presumably formed by the anti-idiotype network or molecular mimicry, is correlated with PACVS symptoms in many patients. Furthermore, the presence of anti-MAS1 antibodies can reduce the efficiency of the ACE2/Angiotensin-(1-7)/MAS1 axis, which normally acts as a counter-regulator. Considering this evidence, an analysis of RAS molecules and the autoantibodies implicated in reactions to them may be useful for evaluating a state of persistent dysregulation associated with post-vaccination symptoms such as asthenia, headache, skin edema and bruising, cardiovascular alterations, and neurovegetative manifestations. Finally, we offer insights into diagnosing these multifaceted syndromes and working hypotheses to guide research into possible therapeutic approaches.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Lung Microbiota in Shaping Host Immunity and Mucosal Vaccine Responses.","authors":"Wael Alturaiki","doi":"10.3390/vaccines14040355","DOIUrl":"https://doi.org/10.3390/vaccines14040355","url":null,"abstract":"<p><p>Respiratory infections remain a leading cause of morbidity and mortality worldwide, highlighting the urgent need to better understand host defense mechanisms in the respiratory tract. Recent advances in sequencing technologies have challenged the traditional view of the lungs as sterile organs and revealed the presence of a distinct, low-biomass microbial community known as the lung microbiota. These microbial populations interact closely with airway epithelial cells and immune cells to maintain respiratory homeostasis and regulate host immune responses. In healthy lungs, microbial communities dominated by Firmicutes, Bacteroidetes, and Proteobacteria contribute to immune regulation through interactions with innate and adaptive immune pathways. Microbiota-derived signals are detected by pattern recognition receptors, activating signaling pathways that regulate cytokine production, immune cell recruitment, and T-cell differentiation. In the respiratory mucosa, microbial stimulation can also induce epithelial and antigen-presenting cells to produce B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL), which promote immunoglobulin A (IgA) class-switch recombination and support mucosal antibody responses. During pulmonary infection, disruption of microbial communities can lead to dysbiosis that amplifies inflammatory responses, impairs epithelial barrier integrity, and increases susceptibility to secondary bacterial infections. In addition to local microbial interactions, the gut-lung axis represents a key communication pathway linking intestinal microbiota with respiratory immunity through microbial metabolites such as short-chain fatty acids (SCFAs) and immune signaling networks. This review summarizes current insights into microbiota-immune crosstalk in the lung during pulmonary infection and discusses how these interactions may inform mucosal vaccine development. A deeper understanding of host-microbiota interactions may enable microbiome-informed vaccines and therapeutic strategies to improve protection against respiratory diseases.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Immune Responses and Safety Profiles Following a Fourth Heterologous Dose (Second Booster) with mRNA-1273 in Individuals Previously Vaccinated with Two Doses of CoronaVac and a Booster Dose of Either AZD1222 or BNT162b2.","authors":"Auchara Tangsathapornpong, Sira Nanthapisal, Waraphon Fukpho, Pornumpa Bunjoungmanee, Yamonbhorn Neamkul, Kanassanan Pontan, Arthit Boonyarangkul, Supattra Wanpen, Kanokporn Thongphubeth, Phuntila Tharabenjasin, Peera Jaru-Ampornpan","doi":"10.3390/vaccines14040348","DOIUrl":"https://doi.org/10.3390/vaccines14040348","url":null,"abstract":"<p><p><i><b>Background/Objectives</b></i>: Our previous study demonstrated that while the third SARS-CoV-2 booster effectively enhanced immunity against the Delta subvariant, its protection declined over time. This study aimed to evaluate and compare the humoral and cellular immune responses, as well as reactogenicity, of the mRNA-1273 vaccine administered as a fourth booster in healthy Thai adults previously vaccinated with two doses of CoronaVac (CV) followed by a third dose of either AZD1222 (AZ) or BNT162b2 (BNT). <i><b>Methods</b></i>: Participants received a single 100 µg (0.5 mL) intramuscular dose of mRNA-1273. Blood samples were collected at baseline (D0), D14, D90, and D180 to assess anti-RBD IgG, conduct a surrogate virus neutralization test (sVNT) against the Delta and Omicron variants, and assess IFN-γ levels and reactogenicity. <i><b>Results</b></i>: Both 2CV/AZ- and 2CV/BNT-primed groups exhibited comparable local and systemic reactogenicity. The fourth mRNA-1273 dose markedly increased Delta variant inhibition within 14 days in both groups and remained at high levels at Days 90 and 180. sVNT inhibition against Omicron rose similarly in both groups at Day 14; it declined sharply by Days 90 and 180, with the 2CV/AZ-primed group showing significantly lower levels than the 2CV/BNT-primed group. Baseline anti-RBD IgG levels were lower in the 2CV/AZ group (<i>p</i> = 0.003) but surpassed those of the 2CV/BNT group by Day 14, with no significant differences at later time points. IFN-γ responses followed a similar pattern to anti-RBD IgG <i><b>Conclusions</b></i>: A heterologous fourth mRNA-1273 booster in both 2CV/AZ- and 2CV/BNT-primed groups effectively enhances B-cell and T-cell responses against SARS-CoV-2. However, emerging variants such as Omicron may still pose challenges. The trial was registered with the Thai Clinical Trials Registry: the name of the registry: \"The comparison of immune response to the 4th dose booster with mRNA-1273 COVID-19 vaccine in individuals who had received 2 doses of CoronaVac and booster with ChAdOx-1 or BNT162b2 COVID-19 vaccine\", TCTR20220205002 on 5 February 2022.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seasonal Influenza Vaccine Uptake, Acceptance and Willingness to Vaccinate in Post-COVID-19 Vaccine Era Among Adult High-Risk Groups in Gulf Cooperation Council Countries (GCC): A Narrative Review of the Literature.","authors":"Moath Aljohani","doi":"10.3390/vaccines14040351","DOIUrl":"https://doi.org/10.3390/vaccines14040351","url":null,"abstract":"<p><strong>Background/objectives: </strong>Reports on seasonal influenza vaccine (SIV) coverage in Gulf Cooperation Council (GCC) countries showed lower than targeted coverage among high-risk populations both before and after the COVID-19 pandemic and subsequent COVID-19 vaccine release. This narrative review aims to synthesise SIV coverage following the introduction of COVID-19 vaccines among at-risk groups in the GCC region.</p><p><strong>Methods: </strong>Database searches included PubMed and Google Scholar for articles assessing SIV uptake, acceptance, hesitancy, and intention to vaccinate among adults in high-risk groups in GCC countries, with data collected after the introduction of COVID-19 vaccines.</p><p><strong>Results: </strong>SIV uptake ranged from 1.8% among pregnant women to 64.1% among dialysis patients in Saudi Arabia. Healthcare workers (HCWs) demonstrated the highest overall coverage, reaching 64.5% for annual uptake in Bahrain, with 79% of HCWs in Saudi Arabia intending to vaccinate. Prevalent barriers included low risk perception and consideration of influenza as a mild disease not necessitating SIV uptake, as well as vaccine effectiveness and safety concerns. Previous vaccination, physician advice, and policy or mandates for HCWs were identified as frequent facilitators of uptake.</p><p><strong>Conclusion: </strong>Suboptimal uptake was reported among most high-risk groups in GCC countries. Health Belief Model components and physician involvement appear to have a significant impact on vaccine uptake among the intended population. More emphasis should be directed toward effective risk communication and action cues methods to enhance uptake among high-risk groups. Future research is needed to cover understudied areas like the elderly aged ≥ 65 years, cancer and other high-risk groups, in addition to further studies for GCC countries other than Saudi Arabia in the post-COVID-19 vaccine period.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Study to Investigate the Safety and Immunogenicity of Monovalent Omicron LP.8.1-Adapted BNT162b2 COVID-19 Vaccine in Adults ≥ 65 Years of Age and High-Risk Adults 18-64 Years of Age (Preliminary Results).","authors":"Rucha Dadhe, Juleen Gayed, Muneeb Iqbal, Rohit Solan, Han Wu, Hua Ma, Xia Xu, Federico J Mensa, Todd Belanger, David Cooper, Robin Mogg, Annaliesa S Anderson, Özlem Türeci, Uǧur Şahin, Pirada Suphaphiphat Allen, Kayvon Modjarrad, Alejandra Gurtman, Kelly Lindert","doi":"10.3390/vaccines14040350","DOIUrl":"https://doi.org/10.3390/vaccines14040350","url":null,"abstract":"<p><strong>Background/objectives: </strong>This study evaluated the Omicron LP.8.1 variant-adapted BNT162b2 mRNA vaccine (LP.8.1-adapted BNT162b2).</p><p><strong>Methods: </strong>This analysis is part of an ongoing phase 3 open-label study evaluating the immunogenicity, safety, and tolerability of LP.8.1-adapted BNT162b2. Reported here are descriptive 2-week post-vaccination results in 18-64 -year-olds at high risk of severe COVID-19 and in ≥65-year-olds who received the Omicron KP.2-adapted COVID-19 vaccine ≥ 6 months previously. Primary immunogenicity endpoints included neutralizing antibody geometric mean titers (GMTs) against LP.8.1 and KP.2 at 2 weeks after vaccination and geometric mean fold rises from baseline to 2 weeks after vaccination. Results were compared with a historical control group of adults who received KP.2-adapted BNT162b2 in a previous study. Tolerability and safety were also assessed.</p><p><strong>Results: </strong>Overall, 104 participants received LP.8.1-adapted BNT162b2 (18-64-year-olds, <i>n</i> = 51; ≥65-year-olds, <i>n</i> = 53). Baseline neutralizing GMTs were higher in LP.8.1-adapted BNT162b2 recipients than in the historical control group of KP.2-adapted BNT162b2 recipients against both sublineages (248 vs. 157 against LP.8.1; 372 vs. 187 against KP.2). Serum-neutralizing LP.8.1 and KP.2 GMTs increased 2 weeks after vaccination with LP.8.1-adapted BNT162b2 (1752 against LP.8.1; 2104 against KP.2) and historical control groups (1555 and 2395, respectively), and across both age groups. Reactogenicity events with LP.8.1-adapted BNT162b2 were generally mild or moderate and occurred at generally similar frequencies in both age groups. Adverse events were reported in 4.8% of participants (all in 18-64-year-olds); no serious adverse events were reported.</p><p><strong>Conclusions: </strong>After 2 weeks of follow-up, and in a small sample size, LP.8.1-adapted BNT162b2 was immunogenic in ≥65-year-olds and ≥18-year-olds at high risk of severe COVID-19. The safety and tolerability profile for LP.8.1-adapted BNT162b2 was consistent with the current US prescribing information for BNT162b2 and that of other variant-adapted BNT162b2 vaccines (Clinicaltrials.gov Identifier: NCT07069309, registered 16 July 2025).</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fine-Mapping and Protective Analysis of Immunodominant Linear B-Cell Epitopes of FimA Antigen of Klebsiella Pneumoniae.","authors":"Pengju Yan, Longlong Chen, Guangyang Ming, Zhifu Chen, Qiang Gou, Yue Yuan, Haiming Jing, Ping Luo, Jinyong Zhang, Zhuo Zhao","doi":"10.3390/vaccines14040347","DOIUrl":"https://doi.org/10.3390/vaccines14040347","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background/Objectives:&lt;/b&gt;&lt;i&gt;Klebsiella pneumoniae&lt;/i&gt; (&lt;i&gt;K. pneumoniae&lt;/i&gt;) is a leading cause of serious hospital-acquired and community-acquired infections, with limited treatment options, especially for immunocompromised and critically ill patients. No licensed vaccine is currently available. The FimA antigen, a key fimbrial subunit essential for bacterial adhesion and invasion, represents a promising vaccine target. However, little is known about the immunodominant antibody responses against invasive &lt;i&gt;K. pneumoniae.&lt;/i&gt; This study aimed to evaluate the immunogenicity and protective efficacy of recombinant FimA protein, to fine-map its immunodominant linear B-cell epitopes, and to assess the individual and combined protective capacity of these epitopes against both standard and clinically isolated &lt;i&gt;K. pneumoniae&lt;/i&gt; strains. &lt;b&gt;Methods:&lt;/b&gt; A murine model of lethal &lt;i&gt;K. pneumoniae&lt;/i&gt; challenge was used. Recombinant FimA protein was administered to evaluate immunogenicity and protective efficacy. Immunodominant linear B-cell epitopes were identified by overlapping peptide ELISA using immune antisera. The identified epitopes were synthesized and conjugated to keyhole limpet hemocyanin (KLH). Mice were immunized with individual epitope-KLH conjugates or a mixture of all four, then challenged with the standard strain ATCC700721 or with multiple clinical isolates of distinct multilocus sequence types (MLST). Epitope-specific antibody responses (total IgG and IgG subclasses) and survival rates were measured. &lt;b&gt;Results:&lt;/b&gt; Immunization with full-length recombinant FimA conferred 90% protection against lethal challenge with the standard strain ATCC700721 and induced robust IgG1-dominant antibody responses. Four novel immunodominant linear B-cell epitopes were identified: FimA&lt;sub&gt;97-114&lt;/sub&gt;, FimA&lt;sub&gt;103-120&lt;/sub&gt;, FimA&lt;sub&gt;109-126&lt;/sub&gt;, and FimA&lt;sub&gt;145-160&lt;/sub&gt;. Structural mapping revealed that the first three epitopes reside within the α-helical region, while FimA&lt;sub&gt;145-160&lt;/sub&gt; is located in the β-sheet domain. These epitopes are highly conserved, exhibiting 100% sequence identity across 36 diverse &lt;i&gt;K. pneumoniae&lt;/i&gt; strains. Among individual epitope-KLH conjugates, FimA&lt;sub&gt;109-126&lt;/sub&gt;-KLH induced the highest epitope-specific antibody titers, followed by FimA&lt;sub&gt;103-120&lt;/sub&gt;-KLH. Immunization with a mixture of all four epitope-KLH conjugates elicited significant cross-protection against multiple clinical isolates, achieving survival rates of 60%, 50%, 50%, and 40% against strains 10CYZ, 13LGY, 19ZXQ, and 22CZY, respectively. Protective immunity was primarily associated with IgG1 subtype responses. &lt;b&gt;Conclusions:&lt;/b&gt; This study provides the first fine-mapping and protective evaluation of immunodominant linear B-cell epitopes within &lt;i&gt;K. pneumoniae&lt;/i&gt; FimA. The identification of highly conserved, functionally relevant B-cell epitopes and the demonstration of cross-protection conferred by a multi-epitope formulatio","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunogenicity and Safety of Extended Dosing Intervals for Pfizer Pentavalent MenABCWY Meningococcal Vaccination in Healthy Adolescents: Results from a Randomized, Phase 2b Study.","authors":"Jake C Jones, Mary D Tipton, Lefteris Zolotas, Jason D Maguire, Kelly Belanger, Yanping Liu, Roger Maansson, Robert E O'Neill, Paul Balmer, Paula Peyrani, Johannes Beeslaar","doi":"10.3390/vaccines14040352","DOIUrl":"https://doi.org/10.3390/vaccines14040352","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Meningococcal disease is primarily caused by serogroups A, B, C, W, and Y. Current US vaccination recommendations include routine serogroup A/C/W/Y (MenACWY) vaccination (ages 11-12 and 16 years) and a two-dose, 0-, 6-month MenB vaccination series (age 16-23 years) based on shared clinical decision-making. Administration of the first-in-class Pfizer pentavalent MenABCWY vaccine (Penbraya^TM), which received US licensure in 2023 as a two-dose, 0-, 6-month series, is endorsed when the MenACWY and MenB vaccines are recommended at the same visit. This study evaluated the immunogenicity and safety of two extended two-dose schedules of MenABCWY in healthy adolescents. <b>Methods:</b> In this observer-blinded, phase 2b study (ClinicalTrials.gov, NCT04440176; 19 June 2020), 309 healthy 11- to 14-year-olds were randomized 1:1 to receive a 0-, 36-month or 0-, 12-month Pfizer MenABCWY schedule, which more closely aligns with current US MenACWY vaccination recommendations. Endpoints included serum bactericidal assay using human complement seroprotection rates (titers ≥ 1:8 or ≥1:16, depending on strain), seroresponse rates (≥4-fold increase from baseline titer), and geometric mean titers (GMTs). Safety was also assessed. <b>Results:</b> One month after the second Pfizer MenABCWY dose, serogroup A/B/C/W/Y seroprotection rates were 100% for the 0-, 36-month schedule and 96.6-100% for the 0-, 12-month schedule; seroresponse rates were 100% and 92.9-100%, respectively. GMTs generally trended higher with the 0-, 36-month schedule. Seroprotection rates through 24 months after the second dose of the 0-, 12-month schedule were 44.0-75.0% for serogroup B and 88.9-100% for serogroup A/C/W/Y). No safety issues were identified. <b>Conclusions:</b> These data support Pfizer MenABCWY dosing flexibility and utility within the current or possible future US meningococcal vaccination framework.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering a Modular PapMV Nanoparticle Vaccine: Comparative Efficacy of a Covalent and a Non-Covalent N-Antigen Vaccine Against Emerging SARS-CoV-2 Variants.","authors":"Léa-J Blanchette, Marilène Bolduc, Tekeleselassie Woldemariam, Mitra Yousefi, Henintsoa Rabezanahary, Santa-M Olivera-Ugarte, Caroline Garneau, Myriam Angers, Rong Shi, Louis Flamand, Mariana Baz, Silvia Vidal, Darryl Falzarano, Jean-François Lemay, Denis Leclerc","doi":"10.3390/vaccines14040349","DOIUrl":"https://doi.org/10.3390/vaccines14040349","url":null,"abstract":"<p><p><b>Background</b>: Despite the effectiveness of current SARS-CoV-2 vaccines, the genetic variability of the viral target has led to the emergence of variants capable of evading vaccine-induced protection. To ensure broader and more durable protection, we investigated the efficacy of a novel vaccine strategy. <b>Methods</b>: This vaccine utilizes the highly conserved nucleocapsid (N) protein as its primary antigen, rather than the spike (S) protein. It incorporates the Papaya Mosaic Virus (PapMV) nanoparticle, a Toll-like receptor (TLR) 7/8 agonist with intrinsic adjuvant properties, as a vaccine platform. <b>Results</b>: The vaccine formulations, comprising PapMV nanoparticles and the N antigen covalently or non-covalently attached to the PpaMV nano, generated robust humoral (antibody) and cellular (T-cell) immune responses. Protective efficacy was evaluated in K18-hACE2 transgenic mice challenged with either the ancestral SARS-CoV-2 strain or the Omicron XBB.1.5 variant. In both cases, the vaccine significantly reduced inflammation and viral titers in the lungs of vaccinated animals. <b>Conclusions</b>: These results highlight the potential of this PapMV-N vaccine to induce broad protection against diverse SARS-CoV-2 variants.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"14 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}