NPJ Vaccines最新文献

{"title":"Epitope specificity of antibody-mediated protection induced in mice by the malaria vaccine RTS,S/AS01.","authors":"Yevel Flores-Garcia, Berenice Salgado-Jimenez, Minah Park, Shamika Mathis-Torres, Emily Locke, Randall S MacGill, Re'em Moskovitz, Ian A Wilson, Fidel Zavala","doi":"10.1038/s41541-025-01162-5","DOIUrl":"10.1038/s41541-025-01162-5","url":null,"abstract":"<p><p>Antibodies induced by the malaria vaccine RTS,S/AS01 neutralize infectivity of transgenic sporozoites expressing Plasmodium falciparum CSP (PfCSP). These antibodies recognize the junctional, minor repeats, central repeats, and C-term regions of this antigen. The epitope specificity of antibodies mediating protection in mice was characterized in vivo using transgenic sporozoites expressing restricted antigenic portions of PfCSP. In this model, we found protection is mediated mostly by antibodies specific for the central repeats.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"101"},"PeriodicalIF":6.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111528","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":"Single cell transcriptomics correlate avian coronavirus prime vaccination efficacy with antigen-presenting cell preference.","authors":"Xuefeng Li, Yumeng Liang, Yu Zhang, Botao Fa, Zheyi Liu, Lu Cui, Miaomiao Xi, Shufeng Feng, Li Xu, Xiaoxiao Liu, Zhengtao Xiao, Shengwang Liu, Hai Li","doi":"10.1038/s41541-025-01154-5","DOIUrl":"10.1038/s41541-025-01154-5","url":null,"abstract":"<p><p>Biosafe and effective vaccines are urgently needed for the prevention and control of avian infectious bronchitis virus (IBV), the first coronavirus to be discovered, despite extensive vaccination for decades. However, their development has been hindered by our limited understanding of prime vaccination, which is crucial for rational vaccine design. Here, we constructed in vivo dynamic single-cell resolution blood immune landscapes of chickens immunized with live-attenuated or inactivated IBV. Bioinformatic analysis together with in vivo examination revealed that live-attenuated and inactivated vaccines reshaped lymphocytes and led to identical compositions through different mechanisms. Inactivated vaccines activate T lymphocytes through dendritic cells with subsequent T lymphocyte-dependent B lymphocyte expansion upon prime vaccination but induce pathogen-specific antibodies only after boost vaccination. Prime vaccination with a live-attenuated vaccine led to an initial preference for monocytes/macrophages as antigen-presenting cells (APCs), followed by extensive activation of the main APCs, which facilitated rapid T lymphocyte expansion and elicited satisfactory humoral immunity. Along with the disparate utilization of APCs, live-attenuated and inactivated vaccines yielded distinct TCR repertoires and triggered different B lymphocyte dynamics despite their similar final BCR repertoires. Furthermore, APC preference correlated with vaccine effectiveness rather than modality, as prime avian influenza vaccination triggered effective adaptive immune responses with the same APC preference as live-attenuated IBV did. This study comprehensively characterized avian coronavirus prime vaccination and highlighted the key role of APC preference.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"99"},"PeriodicalIF":6.9,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094407","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 RBD-Fc mucosal vaccine provides variant-proof protection against SARS-CoV-2 in mice and hamsters.","authors":"Yanjun Zhang, Yan Wu, Meng-Qian Zhang, Haiyue Rao, Zhaoyong Zhang, Xiangyue He, Yiwen Liang, Raoqing Guo, Yaochang Yuan, Jing Sun, Helen M E Duyvesteyn, Elizabeth E Fry, David I Stuart, Jingxian Zhao, XiaoYan Pan, Shu-Lin Liu, Jincun Zhao, Jiandong Huo","doi":"10.1038/s41541-025-01155-4","DOIUrl":"10.1038/s41541-025-01155-4","url":null,"abstract":"<p><p>Current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are effective against severe disease and death, but do not prevent viral infections, probably due to the limited mucosal immunity induced by intramuscular administration of the vaccine. Fusion of SARS-CoV-2 subunit immunogens with a human IgG Fc backbone can be used as a mucosal vaccine but its effectiveness in delivery in animal models, and its immunogenicity and the vaccine-induced protection against viral infections requires further studies. Here we investigate a bivalent RBD-Fc vaccine that includes the spike receptor-binding domains (RBDs) of the ancestral and BQ.1.1 variant of SARS-CoV-2. Ex vivo fluorescent imaging demonstrates that this vaccine can be effectively delivered to the lungs of mice through intranasal administration, with enhancement of retention in the nasal cavity and lung parenchyma. In mice, the vaccine elicited potent and broad-spectrum antibody responses against different variants including KP.3 which could persist for at least 3 months after booster. Importantly, it was able to induce RBD-specific mucosal IgA responses. Further, heterologous intranasal immunisation with adeno-vectored Chadv1 and RBD-Fc elicited both potent neutralising antibody and T cell responses. Immunised BALB/c and K18-hACE2-transgenic mice were also protected against viral challenge of XBB.1 and viral transmission was effectively limited in hamsters through intranasal immunisation. This work thus demonstrates the potential of RBD-Fc antigens as mucosal vaccines for prevention of breakthrough infections and onward transmission. Moreover, Fc-fusion proteins can be used as an effective mucosal vaccine strategy which can be used either alone or in combination with other vaccine technology to constitute heterologous immunisations, enabling strong protection against SARS-CoV-2 and other respiratory viruses.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"100"},"PeriodicalIF":6.9,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094404","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":"Durable T cell immunity to COVID-19 vaccines in MS patients on B cell depletion therapy.","authors":"Julia Davis-Porada, Ceren Tozlu, Claudia Aiello, Sokratis A Apostolidis, Amit Bar-Or, Riley Bove, Diego A Espinoza, Sugeidy Ferreira Brito, Dina Jacobs, Mihir Kakara, Kaho Onomichi, Adelle Ricci, Joseph J Sabatino, Elizabeth Walker, E John Wherry, Lili Zhang, Wen Zhu, Zongqi Xia, Philip De Jager, Sarah Flanagan Wesley, Rebecca Straus Farber, Donna L Farber","doi":"10.1038/s41541-025-01151-8","DOIUrl":"10.1038/s41541-025-01151-8","url":null,"abstract":"<p><p>Immune-mediated protection generated to COVID-19 mRNA vaccines is associated with anti-Spike (S) protein neutralizing antibodies. However, humoral immunity is compromised in B cell depleting (BCD) therapies, used to treat autoimmune diseases such as Multiple Sclerosis (MS). To study the effect of BCD on the durability and protective efficacy of vaccine-induced immunity, we evaluated S-reactive antibodies and T cell responses 1-70 weeks post-vaccination in MS cohorts treated with BCD compared to non-BCD therapies from four centers. BCD-treated participants had significantly reduced antibody levels and enhanced frequencies of S-reactive CD4⁺ and CD8⁺ memory T cells to COVID-19 vaccination compared to the non-BCD group, with some variations among different BCD formulations. T cell memory responses persisted up to 14 months post-vaccination in both BCD and non-BCD cohorts, who experienced similar clinical protection from COVID-19. Together, our results establish a critical role for T cell-mediated immunity in anti-viral protection independent of humoral immunity.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"98"},"PeriodicalIF":6.9,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094406","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":"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}