NPJ Vaccines最新文献

{"title":"Development of bivalent RBD adapted COVID-19 vaccines for broad sarbecovirus immunity.","authors":"Laura A Bruno, Celeste Pueblas Castro, Agostina Demaría, Lineia Prado, Clara G Fascetto Cassero, Lucas M Saposnik, Federico Páez Córdoba, Juan Manuel Rodriguez, Giulia Piccini, Roberta Antonelli, Giulia Lapini, Nigel Temperton, Sabrina A Del Priore, Andres C Hernando Insua, Ingrid G Kaufmann, Julio C Vega, Juan M Flo, Karina A Pasquevich, Lorena M Coria, Juliana Cassataro","doi":"10.1038/s41541-025-01156-3","DOIUrl":"https://doi.org/10.1038/s41541-025-01156-3","url":null,"abstract":"<p><p>COVID-19 vaccine adaptation is critical to respond to continuously emerging SARS-CoV-2 variants with enhanced immune evasion. The ARVAC protein subunit vaccine, based on the receptor binding domain of the spike protein of SARS-CoV-2, has been adapted to XBB.1.5 and JN.1 variants, as monovalent and bivalent formulations. Preclinical studies in mice showed that ARVAC XBB.1.5 and JN.1 monovalent vaccines induced strong neutralizing antibodies against XBB and JN.1 lineages, though with limited efficacy against phylogenetically distant variants. By contrast, bivalent formulations combining Gamma antigen with either XBB.1.5 or JN.1 antigens demonstrated superior cross-neutralizing activity, covering variants from Ancestral to JN.1. Additionally, Gamma-containing bivalent vaccines elicited neutralizing antibodies against SARS-CoV-1, highlighting their potential for broad-spectrum immunity. Cellular immune studies confirmed robust CD4⁺ T cell activation across all formulations. These findings support the continued adaptation of ARVAC to current circulant variants and propose ARVAC bivalent vaccines containing the Gamma antigen as a strategy for induction of pan-sarbecovirus immunity.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"108"},"PeriodicalIF":6.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A VLPs based vaccine protects against Zika virus infection and prevents cerebral and testicular damage.","authors":"Nelson Côrtes, Aline Lira, Jaqueline D Q Silva, Evelyn Carvalho, Wasim A Prates-Syed, Barbara Hamaguchi, Ricardo Durães-Carvalho, Andrea Balan, Niels O S Câmara, Otavio Cabral-Marques, Norbert Pardi, Ester C Sabino, José E Krieger, Gustavo Cabral-Miranda","doi":"10.1038/s41541-025-01163-4","DOIUrl":"https://doi.org/10.1038/s41541-025-01163-4","url":null,"abstract":"<p><p>Still, Zika virus (ZIKV) infection poses a substantial public health risk, especially for pregnant women and their fetuses, as it can result in congenital abnormalities and fetal mortality during pregnancy. Despite significant advances in understanding and combating ZIKV, considerable challenges remain in the fight against this flavivirus. A crucial component of this effort is the development of vaccines, none of which have yet been licensed for human use. Here, we present a comprehensive study of a novel ZIKV vaccine candidate based on virus-like particles (VLPs), designed to provide broad immunological protection against viral infection combined with safety, without the need for additional adjuvants. A self-adjuvanted VLPs-based vaccine displaying the envelope protein domain III (EDIII) of ZIKV was built. The EDIII protein was expressed in E. coli and chemically conjugated to QβVLPs. Immunization of C57BL/6 mice with two doses of the EDIII-QβVLPs vaccine elicited strong EDIII-specific Th1-based immune response. Notably, the vaccine induced neutralizing antibodies and conferred protection in type I IFN receptor-deficient (G129) mice against ZIKV challenge. Furthermore, vaccinated male mice were protected from ZIKV-induced cerebral and testicular damage, critical concerns for ZIKV pathogenesis. These findings suggest that the EDIII-QβVLP vaccine is a promising candidate for preventing ZIKV infection, with potential applications in combatting this and other emerging flaviviruses.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"107"},"PeriodicalIF":6.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144160675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An antigen panel to assess the regional relevance of foot and mouth disease vaccines.","authors":"David J Paton, Ginette Wilsden, Clare Fj Browning, Efrem A Foglia, Antonello Di Nardo, Nick J Knowles, Jemma Wadsworth, Simon Gubbins, Ethel Chitsungo, Cisse Rahamatou Moustapha Boukary, Gelagay Ayelet, Charles S Bodjo, Nick Nwankpa, Emiliana Brocchi, Santina Grazioli, Anna Ludi, Donald P King","doi":"10.1038/s41541-025-01128-7","DOIUrl":"https://doi.org/10.1038/s41541-025-01128-7","url":null,"abstract":"<p><p>Despite widespread use of inactivated vaccines to control foot-and-mouth disease (FMD), there is no systematic approach to demonstrate the regional relevance of these products against the specific serotypes and strains that circulate in endemic countries in Africa and Asia. Failure to adopt independent testing of FMD vaccines has contributed to poor trust in their quality and a lack of investment in vaccination programmes. Therefore, a reference antigen panel representing four serotypes, tailored for East Africa, has been established and used to measure FMDV-specific antibody responses in cattle after administration of FMD vaccines commercially available in the region. This revealed inconsistencies and gaps in cross-neutralisation responses that are evident for some vaccines even after giving booster doses. It is concluded that the East Africa reference antigen panel can be used to evaluate FMD vaccine potency and drive up vaccine quality. Further panels could be developed and deployed for other endemic regions.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"106"},"PeriodicalIF":6.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing Moderna's mRNA-1083 and Pfizer's dual-target mRNA vaccines for influenza and COVID-19.","authors":"Adewunmi Akingbola, Abiodun Adegbesan, Kolade Adegoke, Courage Idahor, Petra Mariaria, Favour Peters, Raolat Adenike Salami, Olajide Ojo, Emmanuel Nwaeze, Owolabi Abdullahi, Joel Chuku","doi":"10.1038/s41541-025-01145-6","DOIUrl":"10.1038/s41541-025-01145-6","url":null,"abstract":"<p><p>This review examines Moderna's mRNA-1083 and Pfizer/BioNTech's mRNA-1020/1030 dual-target vaccines for COVID-19 and influenza. Both utilize mRNA technology, demonstrating strong immunogenicity and favorable safety profiles. Moderna's mRNA-1083 showed superior immune responses, while Pfizer's mRNA-1020/1030 performed well but was slightly less effective against influenza B. These vaccines simplify immunization strategies, enhance protection, and emphasize the need for global vaccine equity to prevent future outbreaks.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"105"},"PeriodicalIF":6.9,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143104","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":"Live attenuated SARS-CoV-2 vaccine OTS-228 demonstrates efficacy, safety, and stability in preclinical model.","authors":"Tobias Britzke, Nico Joël Halwe, Lorenz Ulrich, Angele Breithaupt, G Tuba Barut, Claudia Wylezich, Nadine Ebert, Bettina Salome Trüeb, Volker Thiel, Donata Hoffmann, Martin Beer, Jacob Schön","doi":"10.1038/s41541-025-01165-2","DOIUrl":"10.1038/s41541-025-01165-2","url":null,"abstract":"<p><p>Live attenuated vaccines (LAV) have the potential to meet all the criteria for an efficacious vaccine. In addition to providing protection against the target disease, they offer the potential to prevent transmission, provide cross-protection by stimulating humoral and cellular immunity, and allow versatility in application routes. The SARS-CoV-2 LAV candidate, OTS-228, has demonstrated excellent safety and high efficacy in preclinical models, inducing transmission-blocking immunity and providing full protection, even against variants such as Omicron BA.2, BA.5, and XBB.1.5. However, to ensure that OTS-228 has no dose-dependent side effects and to evaluate potential risk of reversion to virulence-a known general issue with live vaccines-detailed characterization of LAV OTS-228 is essential. To address this, we conducted four different experiments using Syrian hamsters, a model for moderate to severe COVID-19. A maximum dose trial confirmed the vaccine's full attenuation and prevention of transmission, even at high doses. In addition, four intentional serial in vivo passages demonstrated the genomic stability of the vaccine and the non-infectivity of nasal washings. Furthermore, OTS-228 maintained its attenuation and immunogenicity even after 15 additional in vitro passages, providing full protection against lung infection with virulent SARS-CoV-2 strains. Finally, a low-dose experiment confirmed the high efficacy of the vaccine candidate, establishing the protective dose 50 (PD₅₀) at less than 100 TCID₅₀ per hamster. Our results provide strong evidence for the safety and efficacy of the LAV candidate OTS-228 and supports its potential as a safe and effective vaccine in a highly relevant preclinical model.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"104"},"PeriodicalIF":6.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12098885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128376","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":"TnSeq identifies genetic requirements of Mycobacterium tuberculosis for survival under vaccine-induced immunity.","authors":"Kimra S James, Neharika Jain, Kelly Witzl, Nico Cicchetti, Sarah M Fortune, Thomas R Ioerger, Amanda J Martinot, Allison F Carey","doi":"10.1038/s41541-025-01150-9","DOIUrl":"10.1038/s41541-025-01150-9","url":null,"abstract":"<p><p>Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB), remains a persistent global health challenge due to the lack of an effective vaccine. The only licensed TB vaccine, Bacille Calmette-Guerin (BCG), is a live attenuated strain of Mycobacterium bovis that protects young children from severe disease but fails to provide protection through adulthood. It is unclear why BCG provides incomplete protection despite inducing a robust Th1 immune response. We set out to interrogate mycobacterial determinants of vaccine escape using a functional genomics approach, TnSeq, to define bacterial genes required for survival in mice vaccinated with BCG, the live attenuated Mtb vaccine strain, ΔLprG, and in mice with Mtb immunity conferred by prior infection. We find that critical virulence genes associated with acute infection and exponential growth are less essential in hosts with adaptive immunity, including genes encoding the Esx-1 and Mce1 systems. Genetic requirements for Mtb growth in vaccinated and previously Mtb-infected hosts mirror the genetic requirements reported for bacteria under in vitro conditions that reflect aspects of the adaptive immune response. Across distinct immunization conditions, differences in genetic requirements between live attenuated vaccines and vaccination routes are observed, suggesting that different immunization strategies impose distinct bacterial stressors. Collectively, these data support the idea that Mtb requires genes that enable stress adaptation and growth arrest upon encountering the restrictive host environment induced by the adaptive immune response. We demonstrate that TnSeq can be used to understand the bacterial genetic requirements for survival in vaccinated hosts across pre-clinical live attenuated vaccines and therefore may be applied to other vaccine modalities. Understanding how Mtb survives vaccine-induced immunity has the potential to inform the development of new vaccines or adjuvant therapies.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"103"},"PeriodicalIF":6.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12098976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127662","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":"Safety and tolerability of a novel monoclonal antibody cocktail for rabies post-exposure prophylaxis.","authors":"Nidhi Fotedar, Haradanahalli Shankaraiah Ravish","doi":"10.1038/s41541-025-01109-w","DOIUrl":"10.1038/s41541-025-01109-w","url":null,"abstract":"<p><p>Rabies is one of the most lethal viral zoonoses, particularly in low- and middle-income countries where access to post-exposure prophylaxis is limited. Conventional post-exposure prophylaxis relies on rabies immune globulin and vaccination. This study evaluated the safety of a monoclonal antibody cocktail, docaravimab and miromavimab, in 159 patients with severe animal bites. The cocktail was administered locally to 94.3 percent of participants and both locally and systemically to 5.7 percent. Adverse events were reported in 10.7 percent of cases, predominantly mild and local, with no systemic or severe reactions observed. No cases of rabies occurred during six months of follow-up. These findings suggest that the monoclonal antibody cocktail has a favorable safety profile, potentially serving as a viable alternative to traditional rabies immune globulin in post-exposure prophylaxis.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"102"},"PeriodicalIF":6.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119480","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":"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}