NPJ Vaccines最新文献

{"title":"A Plasmodium LARC GAP provides preerythrocytic, stage and species transcending protection in mice.","authors":"Raksha Devi, Rohini Nandi, Satish Mishra","doi":"10.1038/s41541-025-01149-2","DOIUrl":"10.1038/s41541-025-01149-2","url":null,"abstract":"<p><p>Malonyl-CoA-acyl carrier protein transacylase (MCAT) catalyzes the transfer of a malonyl moiety from malonyl-CoA to acyl carrier protein during the initiation step of type II fatty acid synthesis (FASII). The Plasmodium FASII pathway was found to be essential for late liver-stage development in rodent malaria parasites. Here, we generated a novel genetically attenuated parasite (GAP) by disrupting Plasmodium MCAT. Deleting MCAT in rodent malaria parasites did not affect asexual blood-stage propagation and mosquito-stage development. MCAT KO sporozoites failed to initiate blood-stage infection in mice. Hepatic MCAT KO parasites showed impaired nuclear division and apicoplast biogenesis. This led to a defect in hepatic merozoite formation and attenuation of parasites during late liver stages. Vaccination of mice with MCAT KO sporozoites exhibited sterilizing immunity against homologous and heterologous species challenge. Further, MCAT KO-immunized mice were able to clear blood stage infection after iRBCs challenge. These findings highlight that late-liver arresting MCAT KO sporozoite is a promising GAP vaccine candidate for inducing pre-erythrocytic, stage, and species-transcending protection in mice.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"97"},"PeriodicalIF":6.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-related decline in IgM responses associate with reduced opsonophagocytic activity following PCV13 vaccination.","authors":"M Visser, J van Beek, I Tcherniaeva, D M van Rooijen, L Beckers, E Bijvank, M I de Jonge, S P Lockhart, M W Pride, N Rots, D van Baarle, G den Hartog, A M Buisman","doi":"10.1038/s41541-025-01152-7","DOIUrl":"https://doi.org/10.1038/s41541-025-01152-7","url":null,"abstract":"<p><p>Pneumococcal vaccination is crucial in preventing Streptococcus pneumoniae infections in older adults. However, vaccine responses often diminish with age. This study investigates serotype-specific IgM and IgG responses in relation to opsonophagocytic activity (OPA) following thirteen-valent pneumococcal conjugate (PCV13) vaccination in younger (26-49 y; n = 44), middle-aged (50-64 y; n = 71), and older adults (65-98 y; n = 141). Both OPA and IgM responses declined with age, while IgG responses remained relatively stable. In younger adults, post-PCV13 OPA correlated moderate-to-strong with IgM for 8/13 serotypes and with IgG for only 4/13 serotypes. In contrast, middle-aged and older adults showed strong correlations between OPA and both IgM (10/13 serotypes) and IgG (12/13 serotypes). Overall, post-PCV13 OPA was predominantly associated with IgM levels. These observations suggest that declines in IgM, rather than IgG responses, explain reduced PCV13-induced opsonophagocytic activity in aging adults and may inform future vaccination strategies to enhance protection of older adults against pneumococcal disease.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"95"},"PeriodicalIF":6.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human naïve B cells show evidence of anergy and clonal redemption following vaccination.","authors":"Brian L P Dizon, Prasida Holla, Evan C Mutic, Paul Schaughency, Susan K Pierce","doi":"10.1038/s41541-025-01133-w","DOIUrl":"https://doi.org/10.1038/s41541-025-01133-w","url":null,"abstract":"<p><p>In an era of predicted emerging pandemics, the production of effective vaccines may require an in-depth understanding of the biology of human naive B (B_N) cells. Here we provide evidence that the majority of B_N cells expressed CD73, an ecto-5'-nucleotidase often associated with immune cell suppression, and demonstrated features of anergy, including an IgM^lowIgD⁺ surface phenotype, reduced calcium flux in response to IgM crosslinking, and increased PTEN expression. Analysis of antibody sequences encoded by the inherently autoreactive V_H4-34 heavy chain produced by plasmablasts seven days following influenza vaccination showed that in younger but not in older individuals, anergic B_N cells provided a reservoir of B cells capable of responding to vaccination by somatic mutation, resulting in diversification and loss of autoreactivity. These results suggest that effective human vaccines may require the ability to awaken or 'redeem' anergic B_N cells that can be repurposed to participate in pathogen-specific responses.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"96"},"PeriodicalIF":6.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"pS396/pS404 (PHF1) tau vaccine outperforms pS199/pS202 (AT8) in rTg4510 tauopathy model.","authors":"Jonathan P Hulse, Nicole M Maphis, Julianne Peabody, Virginie Bondu, Bryce Chackerian, Kiran Bhaskar","doi":"10.1038/s41541-025-01147-4","DOIUrl":"10.1038/s41541-025-01147-4","url":null,"abstract":"<p><p>Tauopathies, including Alzheimer's disease (AD) and Frontotemporal Dementia (FTD), are histopathologically defined by the aggregation of hyperphosphorylated pathological tau (pTau) as neurofibrillary tangles in the brain. Site-specific phosphorylation of tau occurs early in the disease process and correlates with progressive cognitive decline, thus serving as targetable pathological epitopes for immunotherapy development. Previously, we developed a vaccine (Qβ-pT181) displaying phosphorylated Thr181 tau peptides on the surface of a Qβ bacteriophage virus-like particle (VLP) that induced robust antibody responses, cleared pathological tau, and rescued memory deficits in a transgenic mouse model of tauopathy. Here we report the characterization and comparison of two additional Qβ VLP-based vaccines targeting the dual phosphorylation sites Ser199/Ser202 (Qβ-AT8) and Ser396/Ser404 (Qβ-PHF1). Both Qβ-AT8 and Qβ-PHF1 vaccines elicited high-titer antibody responses against their pTau epitopes. However, only Qβ-PHF1 rescued cognitive deficits, reduced soluble and insoluble pathological tau, and inflammatory microgliosis in a 4.5-month rTg4510 model of FTD. Both sera from Qβ-AT8 and Qβ-PHF1 vaccinated mice were specifically reactive to tau pathology in human AD post-mortem brain sections. These studies further support the use of VLP-based immunotherapies to target pTau in AD and related tauopathies and provide potential insight into the clinical efficacy of various pTau epitopes in the development of immunotherapies.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"94"},"PeriodicalIF":6.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Correction: Establishing a universal IVRP method for quadrivalent HPV vaccines to replace in vivo potency tests.","authors":"Jinpan Hu, Zijing Jia, Meng Wang, Lingling Nie, Wangjun Fu, Qingfeng Zhang, Haiyang Qin, Jianhui Nie, Xiaoyu Xu, Lingjie Xu, Fengze Wang, Yingping Chen, Bo Xing, Tao Li, Danfeng Li, Shaowei Li, Ningshao Xia, Xiangxi Wang, Weijin Huang","doi":"10.1038/s41541-025-01142-9","DOIUrl":"10.1038/s41541-025-01142-9","url":null,"abstract":"","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"93"},"PeriodicalIF":6.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular immune signatures and differences of four porcine circovirus type 2 vaccines to heterologous PCV2d infection.","authors":"Shuai Li, Jiawei Liu, Lingbo Meng, Susu Yin, Hua Wu, Jianwen Zou, Dongbo Yuan, Hairong He, Guanghao Yin, Xianfeng Jia, Xiaoli Hao, Shaobin Shang","doi":"10.1038/s41541-025-01138-5","DOIUrl":"https://doi.org/10.1038/s41541-025-01138-5","url":null,"abstract":"<p><p>Multiple PCV2 vaccines originating from different antigens and formula are commercially available and have shown great effectiveness in protecting pigs from clinical disease. However, our understanding of the immune mechanisms underlying these vaccine-induced protection is fairly limited, except for antibody responses. Head-to-head comparisons of T-cell responses induced by these vaccines in pigs would provide valuable insights into the mechanisms of protective immunity against PCV2. Here, T-cell responses in peripheral blood of pigs after vaccination with four representative PCV2 vaccines, as well as local and systemic recall responses following challenge with a PCV2d strain were examined. All four PCV2 vaccines induce a rapid cellular immune response that could be detected as early as 7 days post-vaccination. Some vaccine-primed CD4 T cells exhibit multifunctionality, being capable of secreting double (IFNγ/TNFα) and even triple cytokines (IFNγ/TNFα/IL-2) simultaneously. In contrast, a weak CD8 T cell response was also detected in the vaccinated pigs but just IFNγ/TNFα double producer and lack of cytotoxicity. These vaccine-activated CD4 and CD8 T cells displayed phenotypes of effector memory or terminally-differentiated effector memory T cells, which rapidly expand to subsequent PCV2d challenges. Prior-vaccinated pigs exhibited a stronger T cell cytokine response post-challenge, being most evident in the spleen. Notably, the cellular immune response induced by different types of PCV2 vaccines exhibited high similarity in phenotypic and functional properties, while showing significant differences in kinetics and magnitude. These results advance our understanding of cell-mediated immune protection afforded by different PCV2 vaccines and unravel fundamental differences in cellular immune response induced by PCV2 vaccines utilizing diverse technologies.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"92"},"PeriodicalIF":6.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global socioeconomic inequalities in vaccination coverage, supply, and confidence.","authors":"Qiang Wang, Kathy Leung, Mark Jit, Joseph T Wu, Leesa Lin","doi":"10.1038/s41541-025-01143-8","DOIUrl":"https://doi.org/10.1038/s41541-025-01143-8","url":null,"abstract":"<p><p>Sustainable Development Goal (SDG) adopted in 2015 aim to reduce inequalities and achieve universal health coverage, including access to essential vaccines for all. Using data from WHO, the Vaccine Confidence Project™, World Bank, and UNDP, we analyzed between-country inequalities in coverage of four vaccines (DTP1, DTP3, MCV1, and POL3), vaccine stock-outs, and vaccine confidence. Economic- and education-related inequalities in coverage (measured by the concentration index) declined from 2015 to 2019, increased in 2020, peaked in 2021, and have declined again since 2022. Inequalities increased continuously in the Region of the Americas. Over 2015-2022, 94 countries/territories reported at least one national level DTP-containing vaccine stock-out. Countries/territories with higher income or education attainment showed lower vaccine confidence. Our study underscores the decrease of inequalities in vaccination coverage following the SDG adoption in most regions, and emphasizes the need to address vaccine stock-outs and strength the vaccine confidence.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"91"},"PeriodicalIF":6.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer type and gene signatures associated with breakthrough infections following COVID-19 mRNA vaccination.","authors":"Youjia Zhong, Jiaqi Li, Ainsley Ryan Yan Bin Lee, Janice Yu Jin Tan, Carina Jing Xuan Tay, Clara Wt Koh, Ethan Yong Tzi Seow, Wee Chee Yap, Shi Yin Wong, Chun En Yau, Chen Ee Low, Kelvin Bryan Tan, Barnaby Edward Young, Yan Su, Arun George Devasia, Perumal Dharuman, Alexander Lezhava, Rahul Pandey, Panneer Selvi Govindaraju, Sidney Yee, Ruifen Weng, Candy Khoo, Shaun Shi Yan Tan, Matilda Lee, Joline Lim, Esther Chan, Carol Lf Ho, Louis Yi Ann Chai, Chee Wah Tan, Soo Chin Lee, Kuan Rong Chan, Raghav Sundar","doi":"10.1038/s41541-025-01141-w","DOIUrl":"https://doi.org/10.1038/s41541-025-01141-w","url":null,"abstract":"<p><p>We used epidemiological data from 21195 patients with cancer and 180407 matched controls, including in-depth analyses in 216 cancer patients, to discover clinical and molecular determinants that predispose cancer patients to breakthrough infections. Patients with B cell malignancies, with differential expression of CD24, CDK14 and PLEKHG1, were most susceptible to breakthrough infections, suggesting that these patients may require more booster immunisations to ameliorate cellular responses and immune protection against COVID-19.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"90"},"PeriodicalIF":6.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An adjuvanted chimeric spike antigen boosts lung-resident memory T-cells and induces pan-sarbecovirus protective immunity.","authors":"Claudio Counoupas, Elizabeth Chan, Paco Pino, Joshua Armitano, Matt D Johansen, Lachlan J Smith, Caroline L Ashley, Eva Estapé, Jean Troyon, Sibel Alca, Stefan Miemczyk, Nicole G Hansbro, Gabriella Scandurra, Warwick J Britton, Thomas Courant, Patrice M Dubois, Nicolas Collin, V Krishna Mohan, Philip M Hansbro, Maria J Wurm, Florian M Wurm, Megan Steain, James A Triccas","doi":"10.1038/s41541-025-01144-7","DOIUrl":"https://doi.org/10.1038/s41541-025-01144-7","url":null,"abstract":"<p><p>Next-generation vaccines are essential to address the evolving nature of SARS-CoV-2 and to protect against emerging pandemic threats from other coronaviruses. These vaccines should elicit broad protection, provide long-lasting immunity and ensure equitable access for all populations. In this study, we developed a panel of chimeric, full-length spike antigens incorporating mutations from previous, circulating and predicted SARS-CoV-2 variants. The lead candidate (CoVEXS5) was produced through a high-yield production process in stable CHO cells achieving >95% purity, demonstrated long-term stability and elicited broadly cross-reactive neutralising antibodies when delivered to mice in a squalene emulsion adjuvant (Sepivac SWE™). In both mice and hamsters, CoVEXS5 immunisation reduced clinical disease signs, lung inflammation and organ viral titres after SARS-CoV-2 infection, including following challenge with the highly immunoevasive Omicron XBB.1.5 subvariant. In mice previously primed with a licenced mRNA vaccine (Comirnaty XBB.1.5, termed mRNA-XBB), CoVEXS5 boosting significantly increased neutralising antibody (nAb) levels against viruses from three sarbecoviruses clades. Boosting with CoVEXS5 via systemic delivery elicited CD4+ lung-resident memory T cells, typically associated with mucosal immunisation strategies, which were not detected following mRNA-XBB boosting. Vaccination of hamsters with CoVEXS5 conferred significant protection against weight loss after SARS-CoV-1 challenge, compared to mRNA-XBB immunisation, that correlated with anti-SARS-CoV-1 nAbs in the sera of vaccinated animals. These findings highlight the potential of a chimeric spike antigen, formulated in an open-access adjuvant, as a next-generation vaccine candidate to enhance cross-protection against emerging sarbecoviruses in vaccinated populations globally.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"89"},"PeriodicalIF":6.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide association study of myocarditis and pericarditis following COVID-19 vaccination.","authors":"Marco Cavalli, Niclas Eriksson, Tomasz Baron, Ahmet Yalcinkaya, Nils Landegren, Petter Brodin, Pär Hallberg, Mia Wadelius","doi":"10.1038/s41541-025-01139-4","DOIUrl":"https://doi.org/10.1038/s41541-025-01139-4","url":null,"abstract":"<p><p>This genome-wide association study (GWAS) explores the genetic components of severe adverse events following COVID-19 vaccination, with focus on myocarditis and pericarditis. Three SNPs (rs536572545, rs146289966 and rs142297026) near the SCAF11 gene were linked to pericarditis, while rs570375365 in the LRRC4C gene was associated with myocarditis. These findings suggest that genetic variants may influence inflammation pathways, providing a basis for further investigation into the immunological responses triggered by vaccines.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"88"},"PeriodicalIF":6.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}