{"title":"Next-gen novel nanocage-based multivalent vaccine candidate to tackle the rising menace of Mpox.","authors":"Rahul Ahuja, Preeti Vishwakarma, Varun Kumar, Ritika Khatri, Ananya Chatterjee, Surbhi Mishra, Zaigham Abbas Rizvi, Anup Singh, Gurleen Kaur, Vikas Maithil, Kunal Tarane, Akanksha Chauhan, Sarjeet Singh, Pooja Yadav, Devendra Yadav, Sangita Kumari Sinha, Syed Khalid Ali, Abhisek Chatterjee, Priyanka Priyadarsiny, Amit Awasthi, Vidya Mangala Prasad, Shubbir Ahmed, Sweety Samal","doi":"10.1038/s41541-025-01174-1","DOIUrl":"10.1038/s41541-025-01174-1","url":null,"abstract":"<p><p>The recent emergence and global spread of the human Monkeypox virus (MPXV), including its transmission to non-endemic regions, have raised significant global health concerns. In this proof-of-concept study, we developed a recombinant protein-based MPXV vaccine candidate, employing an innovative and versatile multivalent, self-assembled nanocage protein scaffold. Two immunogenic antigens derived from the contemporary circulating MPXV strain have been incorporated into a self-assembled non-structural protein-10 (NSP-10) scaffold, expressed, and purified using an Escherichia coli expression system without a purification tag. The vaccine candidate elicited strong antibody responses in mice and conferred protection against the lethal Vaccinia virus in an intranasal and skin pock in vivo study. Additionally, an intranasal challenge with the MPXV strain clade IIb in immunized mice demonstrated promising outcomes, including a significant reduction in viral titres and eliciting a robust neutralizing antibody response. This study demonstrates a feasible, scalable, and cost-effective approach for the development of the MPXV vaccine.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"117"},"PeriodicalIF":6.9,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248943","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}
NPJ VaccinesPub Date : 2025-06-06DOI: 10.1038/s41541-025-01167-0
Elisa Fuentes, Chenjerai Jairoce, Didac Macià, Leonie Mayer, Jorge P Torres-Yaguana, Marta Vidal, Rebeca Santano, David L Narum, David Cavanagh, Benoit Gamain, Ross L Coppel, James G Beeson, Sheetij Dutta, Jahit Sacarlal, Ruth Aguilar, Gemma Moncunill, Carlota Dobaño
{"title":"Role of malaria exposure and off-target responses on RTS,S/AS02<sub>A</sub> vaccine immunogenicity and protection in Mozambican children.","authors":"Elisa Fuentes, Chenjerai Jairoce, Didac Macià, Leonie Mayer, Jorge P Torres-Yaguana, Marta Vidal, Rebeca Santano, David L Narum, David Cavanagh, Benoit Gamain, Ross L Coppel, James G Beeson, Sheetij Dutta, Jahit Sacarlal, Ruth Aguilar, Gemma Moncunill, Carlota Dobaño","doi":"10.1038/s41541-025-01167-0","DOIUrl":"10.1038/s41541-025-01167-0","url":null,"abstract":"<p><p>RTS,S/AS01<sub>E</sub> is the first malaria vaccine implemented for young African children. However, it provides partial protection against Plasmodium falciparum (Pf) malaria, and a better understanding of the mechanisms and determinants of vaccine immunity will help develop second-generation improved vaccines. We measured IgG to vaccine target and Pf blood-stage off-target proteins before and after vaccination in 874 children aged 1-4 years in a phase 2b trial of RTS,S/AS02<sub>A</sub> in Mozambique. We found that naturally acquired PfCSP IgG levels pre-vaccination were positively associated with RTS,S immunogenicity. Increased levels of IgG to the C-terminus and NANP-repeat regions of PfCSP, and to PfMSP5 and PfMSP1 block 2, following vaccination, were significantly associated with a lower hazard of clinical malaria over 6 months. Thus, immune priming, anti-PfCSP C-terminus and off-target antibody responses contributed to malaria protection after adjusting for prior Pf exposure, and this could guide strategies for optimizing the immunogen and vaccine deployment.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"116"},"PeriodicalIF":6.9,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234666","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}
NPJ VaccinesPub Date : 2025-06-05DOI: 10.1038/s41541-025-01178-x
Dongrong Yi, Qian Liu, Saisai Guo, Quanjie Li, Yongxin Zhang, Ning Li, Qili Zhang, Kai Lv, Ni An, Lu Han, Hua Chen, Yi Wang, Chunyan Chang, Huihan Shao, Jing Wang, Xiaoyu Li, Linlin Bao, Dayan Wang, Guoyang Liao, Chunjian Huang, Weiguo Zhang, Yijie Dong, Yuelong Shu, Shan Cen
{"title":"Chimeric hemagglutinin and M2 mRNA vaccine for broad influenza subtype protection.","authors":"Dongrong Yi, Qian Liu, Saisai Guo, Quanjie Li, Yongxin Zhang, Ning Li, Qili Zhang, Kai Lv, Ni An, Lu Han, Hua Chen, Yi Wang, Chunyan Chang, Huihan Shao, Jing Wang, Xiaoyu Li, Linlin Bao, Dayan Wang, Guoyang Liao, Chunjian Huang, Weiguo Zhang, Yijie Dong, Yuelong Shu, Shan Cen","doi":"10.1038/s41541-025-01178-x","DOIUrl":"10.1038/s41541-025-01178-x","url":null,"abstract":"<p><p>Since multiple and unpredicted influenza viruses cause seasonal epidemics and even high-risk pandemics, developing a universal influenza vaccine is essential to provide broad protection against various influenza subtypes. Combined with the mRNA lipid nanoparticle-encapsulated (mRNA-LNP) vaccine platform and chimeric immunogen strategy, we developed a novel cocktail mRNA vaccine encoding chimeric HAs (cH5/1-BV, cH7/3) and intact M2 (termed Fluaxe), which confers broad protection against major circulating IAVs and IBVs, as well as highly pathogenic avian influenza. Two-dose intramuscular immunization of Fluaxe in mice elicited cross-reactive neutralizing antibodies, T cell responses, and long-lived immunity, resulting in robust protection against multiple lethal influenza virus infections and severe acute lung injuries. In particular, intramuscular administration stimulated systemic immunity together with a prominent lung tropism of memory cells. Moreover, Fluaxe immunization inhibited the inflammatory response induced by influenza infection. In summary, we conclude that Fluaxe can elicit broad cross-protection against numerous influenza subtypes.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"113"},"PeriodicalIF":6.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234664","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":"Characterization of a suspension Vero cell line for viral vaccine production.","authors":"Léa Bourigault, Corinne Bresson, Christian Jean, Christophe Chevalard, Mathilde Kloutz, Damien Soulet, Fleurine Pelissier, Stéphanie Richard, Isabelle Bassard, Nicolas Sève, Cédric Charretier, Bertrand Pain","doi":"10.1038/s41541-025-01157-2","DOIUrl":"10.1038/s41541-025-01157-2","url":null,"abstract":"<p><p>Vero cells, as approved by the World Health Organization, have been the most commonly used continuous cell line for viral vaccine production over the last 25 years, but their adherent phenotype continues to limit productivity. Adapting to a suspension culture would overcome this restriction and reduce production costs. First, a Vero suspension isolate was obtained and metabolically characterized. Second, RNA sequencing analysis was used to identify differentially expressed genes between adherent and suspension cells, which revealed complete downregulation of adhesion and matrix-associated genes. Additionally, signaling pathways involving Wnt and other tyrosine kinase receptors were identified as potential leads for growth optimization. In particular, supplementation with fibroblast growth factor 2 allowed for a 20% increase in cell density. Finally, a comparative viral productivity assay revealed a 30% increase in poliovirus production in suspension Vero cells compared to adherent cells depending on the serotype, as well as a 140% increase in respiratory syncytial virus production and a 150% increase in yellow fever virus production. This work establishes the potential of the suspension Vero cell line as a new cell platform for viral vaccine production.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"114"},"PeriodicalIF":6.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234663","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}
NPJ VaccinesPub Date : 2025-06-05DOI: 10.1038/s41541-025-01180-3
M Visser, D M van Rooijen, J Wolf, L Beckers, M Ohm, M I de Jonge, A M Buisman, G den Hartog
{"title":"Immunogenicity of primary and booster MenACWY-TT vaccination in older adults and the importance of IgM.","authors":"M Visser, D M van Rooijen, J Wolf, L Beckers, M Ohm, M I de Jonge, A M Buisman, G den Hartog","doi":"10.1038/s41541-025-01180-3","DOIUrl":"10.1038/s41541-025-01180-3","url":null,"abstract":"<p><p>Adults aged 65 years and older are at increased risk for infectious diseases, including invasive meningococcal disease (IMD), yet data on meningococcal vaccine immunogenicity in this population remain limited. In this randomized clinical trial (CTIS: 2024-513640-29-00, 13-05-2024), 222 older adults (65-85 years) received a quadrivalent meningococcal conjugate vaccine (MenACWY-TT), with 104 adults receiving a booster dose one year later. Serum bactericidal activity (rSBA) and polysaccharide-specific IgG and IgM concentrations were assessed. One month post-primary vaccination, 91-98% of participants had protective rSBA titers (≥8). Booster vaccination transiently increased bactericidal responses, but titers returned to pre-booster values within a year for MenC, -W, and -Y. rSBA titers correlated stronger with IgM than IgG, particularly for MenW and -Y. Interestingly, IgM depletion markedly reduced rSBA titers, while IgG depletion had minimal impact. These findings highlight that MenACWY-TT vaccination elicits functional antibody responses in older adults, largely driven by IgM.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"115"},"PeriodicalIF":6.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234665","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}
NPJ VaccinesPub Date : 2025-06-03DOI: 10.1038/s41541-025-01166-1
Abhinay Gontu, Sougat Misra, Shubhada K Chothe, Santhamani Ramasamy, Padmaja Jakka, Maurice Byukusenge, Lindsey C LaBella, Meera Surendran Nair, Bhushan M Jayarao, Marco Archetti, Ruth H Nissly, Suresh V Kuchipudi
{"title":"Trans amplifying mRNA vaccine expressing consensus spike elicits broad neutralization of SARS CoV 2 variants.","authors":"Abhinay Gontu, Sougat Misra, Shubhada K Chothe, Santhamani Ramasamy, Padmaja Jakka, Maurice Byukusenge, Lindsey C LaBella, Meera Surendran Nair, Bhushan M Jayarao, Marco Archetti, Ruth H Nissly, Suresh V Kuchipudi","doi":"10.1038/s41541-025-01166-1","DOIUrl":"10.1038/s41541-025-01166-1","url":null,"abstract":"<p><p>SARS-CoV-2 continues to evolve and evade vaccine immunity necessitating vaccines that offer broad protection across variants. Conventional mRNA vaccines face cost and scalability challenges, prompting the exploration of alternative platforms like trans-amplifying (TA) mRNA that offer advantages in safety, manufacturability, and antigen dose optimization. Using consensus sequence of immunodominant antigens is a promising antigen design strategy for board cross-protection. Combining these two features, we designed and evaluated a TA mRNA vaccine encoding a consensus spike protein from SARS-CoV-2. Mice receiving the TA mRNA vaccine produced neutralizing antibody levels comparable to a conventional mRNA vaccine using 40 times less antigen mRNA. In hACE2 transgenic mice challenged with the Omicron BA.1 variant, the TA mRNA vaccine reduced lung viral titers by over 10-fold and induced broadly cross-neutralizing antibodies against multiple variants. These findings highlight the potential of TA mRNA vaccines with consensus antigen design, to improve efficacy and adaptability against SARS-CoV-2 variants.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"110"},"PeriodicalIF":6.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12134344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216418","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}
NPJ VaccinesPub Date : 2025-06-02DOI: 10.1038/s41541-025-01148-3
Wasim Aluísio Prates-Syed, Dennyson Leandro Mathias da Fonseca, Shahab Zaki Pour, Aline Lira, Nelson Cortes, Jaqueline Dinis Queiroz Silva, Evelyn Carvalho, Igor Salerno Filgueiras, Tania Geraldine Churascari Vinces, Lena F Schimke, Lorena C S Chaves, Gerhard Wunderlich, Ricardo Durães-Carvalho, Haroldo Dutra Dias, Hans D Ochs, Niels O S Câmara, Helder I Nakaya, José E Krieger, Otavio Cabral-Marques, Gustavo Cabral-Miranda
{"title":"COVID-19 vaccination atlas using an integrative systems vaccinology approach.","authors":"Wasim Aluísio Prates-Syed, Dennyson Leandro Mathias da Fonseca, Shahab Zaki Pour, Aline Lira, Nelson Cortes, Jaqueline Dinis Queiroz Silva, Evelyn Carvalho, Igor Salerno Filgueiras, Tania Geraldine Churascari Vinces, Lena F Schimke, Lorena C S Chaves, Gerhard Wunderlich, Ricardo Durães-Carvalho, Haroldo Dutra Dias, Hans D Ochs, Niels O S Câmara, Helder I Nakaya, José E Krieger, Otavio Cabral-Marques, Gustavo Cabral-Miranda","doi":"10.1038/s41541-025-01148-3","DOIUrl":"10.1038/s41541-025-01148-3","url":null,"abstract":"<p><p>The COVID-19 vaccinations have played a significant role in controlling the pandemic. To elucidate their impact on the immune system, a COVID-19 vaccination atlas was developed using an integrative systems vaccinology approach. The atlas includes 562 samples from 245 participants, including both healthy individuals and those infected with or without prior vaccination, and covers the administration of five vaccines in different regimens. Key findings include the identification of distinct immune markers that differentiate between vaccine types and infection statuses. We observed that mRNA vaccines induced transient but strong immune responses after booster doses, whereas viral vector vaccines showed sustained immune activation with infection, partially resembling the immune profile exhibited during infection. Heterologous vaccination regimens demonstrated enhanced immune diversification compared to homologous regimens. Finally, we described the immunological landscape of COVID-19 vaccines and vaccines against other pathogens, at the gene-level and in cell population dynamics.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"111"},"PeriodicalIF":6.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209049","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}
NPJ VaccinesPub Date : 2025-06-02DOI: 10.1038/s41541-025-01171-4
Daniel A Wychrij, Taylor I Chapman, Emily Rayens, Whitney Rabacal, Hubertine M E Willems, Kwadwo O Oworae, Brian M Peters, Karen A Norris
{"title":"Protective efficacy of the pan-fungal vaccine NXT-2 against vulvovaginal candidiasis in a murine model.","authors":"Daniel A Wychrij, Taylor I Chapman, Emily Rayens, Whitney Rabacal, Hubertine M E Willems, Kwadwo O Oworae, Brian M Peters, Karen A Norris","doi":"10.1038/s41541-025-01171-4","DOIUrl":"10.1038/s41541-025-01171-4","url":null,"abstract":"<p><p>Vulvovaginal candidiasis (VVC) is the most common clinical manifestation of candidiasis, affecting 75% of women. Despite high incidence rates, increasing drug resistance, and potential teratogenic effects of current treatments, there are no approved fungal vaccines. Previously, we generated a recombinant 'pan-fungal' vaccine candidate, NXT-2, which demonstrated protection against multiple fungal infections including invasive candidiasis. Here, we evaluated the protective efficacy of NXT-2 against Candida albicans in a murine VVC model. NXT-2 was highly immunogenic, eliciting localized immune responses in the vaginal mucosa. NXT-2 immunized mice had reduced fungal burden and polymorphonuclear neutrophil (PMN) recruitment into the vaginal lumen following C. albicans challenge compared to sham immunized mice. PMNs in the vaginal lumen of NXT-2 immunized mice were associated with C. albicans hyphae, which was absent in controls. NXT-2 immunization reduces vaginal tissue damage and inflammation, while providing antibody-mediated protection, demonstrating the potential of the vaccine for the prevention of VVC.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"112"},"PeriodicalIF":6.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209050","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}
NPJ VaccinesPub Date : 2025-05-30DOI: 10.1038/s41541-025-01164-3
Thomas Tipih, Shanna S Leventhal, Kimberly Meade-White, Matthew Lewis, Trenton Bushmaker, Carl Shaia, Andrea Marzi, Heinz Feldmann, David W Hawman
{"title":"Single dose VSV-based vaccine protects mice against lethal heterologous Crimean-Congo hemorrhagic fever virus challenge.","authors":"Thomas Tipih, Shanna S Leventhal, Kimberly Meade-White, Matthew Lewis, Trenton Bushmaker, Carl Shaia, Andrea Marzi, Heinz Feldmann, David W Hawman","doi":"10.1038/s41541-025-01164-3","DOIUrl":"10.1038/s41541-025-01164-3","url":null,"abstract":"<p><p>Crimean-Congo hemorrhagic fever virus (CCHFV) causes a severe, sometimes fatal hemorrhagic fever (CCHF) in humans. Currently, there are no approved therapies against CCHF. In this study we used the recombinant vesicular stomatitis virus (VSV) platform to generate live-attenuated recombinant CCHF vaccine candidates expressing the CCHFV nucleoprotein (NP) and glycoprotein precursor (GPC). As one approach, we utilized the established VSV expressing the full-length Ebola virus glycoprotein (VSV-EBOV) or a truncated version of the EBOV glycoprotein and added the CCHFV-NP (VSV-CCHFnp1 or VSV-CCHFnp2, respectively). Additionally, we prepared a vaccine candidate, VSV-CCHFgpc, in which the VSV glycoprotein was replaced with the CCHFV-GPC. Vaccine constructs induced CCHFV-specific IgG antibodies comprising largely IgG2c subclass. Only, the VSV-CCHFgpc vaccine candidate induced significant T cell immune responses directed against epitopes in the CCHFV-NSm and Gc proteins. Efficacy of the vaccine candidates was evaluated using a prime-only approach in a transiently immune-suppressed mouse model. Animals vaccinated with VSV-CCHFnp2 succumbed to lethal CCHFV challenge, while the VSV-CCHFgpc vaccine candidate afforded partial protection. In contrast, vaccination with VSV-CCHFnp1 uniformly protected animals against death. Our results demonstrate the promise of VSV-CCHFnp1 as a vaccine candidate for CCHFV and warrant continued development.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"109"},"PeriodicalIF":6.9,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187387","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}
NPJ VaccinesPub Date : 2025-05-29DOI: 10.1038/s41541-025-01156-3
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
{"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":"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<sup>+</sup> 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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122808/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}