NPJ VaccinesPub Date : 2025-07-24DOI: 10.1038/s41541-025-01232-8
Dean Porter, Catherine Collins, Andrea Mazzolini, Luc Jouneau, Vanessa Mhanna, Céline Coiffier, Mathilde Peruzzi, Yan Jaszczyszyn, Encarnita Mariotti-Ferrandiz, Francois Huetz, Bertrand Collet, Thierry Mora, Aleksandra M Walczak, Bernard Verrier, Pierre Boudinot
{"title":"Divergent B-cell repertoire remodelling by mRNA, DNA and live attenuated vaccines in fish.","authors":"Dean Porter, Catherine Collins, Andrea Mazzolini, Luc Jouneau, Vanessa Mhanna, Céline Coiffier, Mathilde Peruzzi, Yan Jaszczyszyn, Encarnita Mariotti-Ferrandiz, Francois Huetz, Bertrand Collet, Thierry Mora, Aleksandra M Walczak, Bernard Verrier, Pierre Boudinot","doi":"10.1038/s41541-025-01232-8","DOIUrl":"10.1038/s41541-025-01232-8","url":null,"abstract":"<p><p>Vaccination is critical for the future of aquaculture, and nucleic acid vaccines have a major potential for fighting emerging fish infectious diseases, yet their mechanisms remain poorly understood. We compared B-cell responses induced by an mRNA, a DNA, and an attenuated vaccine, all encoding the same antigen against a fish rhabdovirus. Rainbow trout IgHμ repertoires were examined to investigate how vaccines reshape clonal composition and complexity of the B-cell repertoire. The attenuated virus drove protection through a small number of highly shared public clonotypes encoding neutralizing antibodies. The mRNA vaccine profoundly remodelled the repertoire in some individuals and induces low, but still protective, neutralising Ab titers without public expansions. The DNA vaccine induced high neutralizing Ab titers, providing full protection with minimal impact on B-cell repertoire. Clustering analysis revealed partial sharing of private responses between fish. These findings highlight profound divergences between fish B-cell responses to nucleic acid and attenuated vaccines whilst all of three vaccines induce protective responses.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"166"},"PeriodicalIF":6.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708342","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 : 2025-07-24DOI: 10.1038/s41541-025-01227-5
Chun Chen, Olivia E Benson, Taylor Simmons, Chris L Dorsett, Katarzyna W Janczak, Matthew J Wiest, Mohammad Farazuddin, James R Baker, Pamela T Wong, Jessica J O'Konek
{"title":"Rational adjuvant selection for the neonatal period shapes unique and lasting immune polarization in mice.","authors":"Chun Chen, Olivia E Benson, Taylor Simmons, Chris L Dorsett, Katarzyna W Janczak, Matthew J Wiest, Mohammad Farazuddin, James R Baker, Pamela T Wong, Jessica J O'Konek","doi":"10.1038/s41541-025-01227-5","DOIUrl":"10.1038/s41541-025-01227-5","url":null,"abstract":"<p><p>A major knowledge gap exists in understanding immune effects of adjuvants in early life. As environmental stimuli shape the infant immune system, adjuvants may also influence this process. Using a neonatal mouse model, we investigated the differential effects of adjuvants in neonates vs. adults. Mice were immunized with an adjuvanted hepatitis B vaccine followed by exposure to ovalbumin to determine whether prior immunization alters subsequent heterologous immune responses. Neonatal immunization with a Th2-biased alum-adjuvanted vaccine predisposed mice to develop Th2-biased immunity to subsequent ovalbumin exposures. Conversely, neonatal immunization with a Th1-polarizing CpG-adjuvanted vaccine resulted in preferential priming of Th1-biased heterologous responses. Immunization in adulthood did not alter heterologous immune responses. Early-life immunization modified the ability of bone marrow DCs to prime Th1/Th2 immune responses, suggesting a role for immune training in these antigen agnostic effects. These data suggest that rational adjuvant selection for early-life vaccines may beneficially shape immune development.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"165"},"PeriodicalIF":6.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708344","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":"Precocious Eimeria magna transgenically expressing RHDV P2 subdomain induces immune responses in rabbits.","authors":"Wenxuan Chen, Jingxia Suo, Jiahua Kong, Chunxia Lu, Xiaomin Ge, Fang Yu, Xinming Tang, Xun Suo, Xianyong Liu","doi":"10.1038/s41541-025-01223-9","DOIUrl":"10.1038/s41541-025-01223-9","url":null,"abstract":"<p><p>Rabbit coccidiosis and rabbit haemorrhagic disease (RHD) pose major threats to the rabbit industry, causing significant economic losses. Developing a multivalent vaccine to concurrently protect rabbits against Eimeria and RHDV infections would provide dual protection through a single immunization protocol. Here, we utilized a precocious line of E. magna (EmagPWT) as a vaccine vector to express P2 subdomain of RHDV capsid protein VP60. We constructed three transgenic parasites expressing (i) RHDV1-P2 subdomain, (ii) RHDV2-P2 subdomain, and (iii) 2 copies of P2 subdomains from both RHDV1 and RHDV2. We found that all transgenic parasites elicited detectable neutralizing antibodies and robust mucosal immune response following secondary immunization. In conclusion, our results indicate genetically manipulated precocious Eimeria parasite expressing heterologous antigens, such as P2 subdomain, holds promise as a vector for developing a multivalent vaccine against RHD and Eimeria infections in rabbits.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"167"},"PeriodicalIF":6.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12290045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708343","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":"Long-term efficacy of an inactivated H5N1 whole-particle influenza vaccine in nonhuman primates.","authors":"Misako Nakayama, Naoko Kitagawa, Cong Thanh Nguyen, Takako Sasamura, Kyoko Takashima, Hirohito Ishigaki, Hideaki Ishida, Saori Suzuki, Yoshihiro Sakoda, Mai Quynh Le, Hiroshi Kida, Kazumasa Ogasawara, Yasushi Itoh","doi":"10.1038/s41541-025-01221-x","DOIUrl":"10.1038/s41541-025-01221-x","url":null,"abstract":"<p><p>Outbreaks of H5 highly pathogenic avian influenza A viruses (HPAIVs) in animals pose a threat to humans immunologically naïve to avian influenza viruses. However, annual vaccination, such as for seasonal influenza is not planned because the number of human patients infected with H5 HPAIVs is small, and the possibility of human-to-human transmission of H5 HPAIVs is low at present. However, various clades of H5 HPAIVs have emerged continuously. Therefore, a vaccine that confers long-term and cross-clade immunity is required. To examine the long-term effectiveness and cross-clade reactivity of an H5 influenza virus vaccine, cynomolgus macaques were infected with an H5N1 HPAIV 5 years after two subcutaneous vaccinations with inactivated H5N1 whole-virus particles (H5 clade classical/outlier), which showed higher immunogenicity than did split vaccines in our previous studies. Neutralization titers against the vaccine strain were maintained for 5 years, and a recall immune response was observed on challenge infection against the challenge strain (clade 1) and other H5N1 HPAIV strains (clades 2.2, 2.3.2.1, and 2.3.4.4b). Compared with unvaccinated macaques, viral titers were low, and the cytokine signaling pathways related to the pathogenesis of an influenza virus infection were not activated in the vaccinated macaques. Thus, a whole-virus particle vaccine induced long-term memory sufficient to prevent severe pneumonia caused by an H5N1 HPAIV in cynomolgus macaques.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"164"},"PeriodicalIF":6.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12287460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699050","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 : 2025-07-23DOI: 10.1038/s41541-025-01212-y
Rebecca K McLean, Miriam Pedrera, Nazia Thakur, Ahmed M E Elrefaey, Sophia Hodgson, Sue Lowther, Tristan Reid, Shawn Todd, Brenton Rowe, Jemma Bergfeld, Lee Trinidad, Sarah Riddell, Sarah Edwards, Jean Payne, Jennifer Barr, Nick Rye, Matt Bruce, Tim Poole, Sheree Brown, Toni Dalziel, Gough Au, Megan Fisher, Rachel Layton, Teresa Lambe, Keith Chappell, Ariel Isaacs, Daniel Watterson, Mercedes Mourino, Ruediger Raue, Ireen Sultana Shanta, Ayesha Siddika, Mst Noorjahan Begum, Sezanur Rahman, Abdulla Al Mamun Bhuyan, Muntasir Alam, Mohammed Ziaur Rahman, Mustafizur Rahman, Elma Tchilian, Sarah C Gilbert, Paul Young, Dalan Bailey, Glenn A Marsh, Simon P Graham
{"title":"Nipah virus vaccines evaluated in pigs as a 'One Health' approach to protect public health.","authors":"Rebecca K McLean, Miriam Pedrera, Nazia Thakur, Ahmed M E Elrefaey, Sophia Hodgson, Sue Lowther, Tristan Reid, Shawn Todd, Brenton Rowe, Jemma Bergfeld, Lee Trinidad, Sarah Riddell, Sarah Edwards, Jean Payne, Jennifer Barr, Nick Rye, Matt Bruce, Tim Poole, Sheree Brown, Toni Dalziel, Gough Au, Megan Fisher, Rachel Layton, Teresa Lambe, Keith Chappell, Ariel Isaacs, Daniel Watterson, Mercedes Mourino, Ruediger Raue, Ireen Sultana Shanta, Ayesha Siddika, Mst Noorjahan Begum, Sezanur Rahman, Abdulla Al Mamun Bhuyan, Muntasir Alam, Mohammed Ziaur Rahman, Mustafizur Rahman, Elma Tchilian, Sarah C Gilbert, Paul Young, Dalan Bailey, Glenn A Marsh, Simon P Graham","doi":"10.1038/s41541-025-01212-y","DOIUrl":"10.1038/s41541-025-01212-y","url":null,"abstract":"<p><p>Nipah virus (NiV) causes a severe neurological disease in humans. The first NiV outbreak, in Malaysia, involved pig-to-human transmission, that resulted in significant economic losses to the local pig industry. Despite the risk NiV poses to pig-dense regions, no licensed vaccines exist. This study therefore assessed three NiV vaccine candidates in pigs: (1) adjuvanted soluble NiV (s)G protein, (2) adjuvanted pre-fusion stabilised NiV (mcs)F protein, and (3) adenoviral vectored NiV G (ChAdOx1 NiV G). NiV sG induced the strongest neutralising antibody response, NiV mcsF induced antibodies best able to neutralise cell-cell fusion, whereas ChAdOx1 NiV G elicited CD8<sup>+</sup> T-cell responses. Despite differences in immunogenicity, prime-boost immunisation with all candidates conferred a high degree of protection against NiV infection. Follow-up studies demonstrated longevity of immune responses and broadly comparable immune responses in Bangladeshi pigs under field conditions. These studies provide a platform for developing a NiV vaccine for pigs.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"163"},"PeriodicalIF":6.9,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12287429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699051","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 : 2025-07-22DOI: 10.1038/s41541-025-01222-w
Jing Wang, Kaixing Wu, Yu Liu, Shiyao Wang, Li Zhao, Donghui Zhang, Runhui Liu, Yuhong Ren, Shuai Shao, Qin Liu
{"title":"Development of an mRNA vaccine encoding IHNV glycoprotein protects rainbow trout (Oncorhynchus mykiss) from infection.","authors":"Jing Wang, Kaixing Wu, Yu Liu, Shiyao Wang, Li Zhao, Donghui Zhang, Runhui Liu, Yuhong Ren, Shuai Shao, Qin Liu","doi":"10.1038/s41541-025-01222-w","DOIUrl":"10.1038/s41541-025-01222-w","url":null,"abstract":"<p><p>mRNA vaccines have demonstrated significant potential in preventing human diseases and controlling livestock infections. However, the application of mRNA vaccines in aquaculture, especially on fish, remains limited. Infectious hematopoietic necrosis virus (IHNV) is an RNA virus that mainly affects rainbow trout (Oncorhynchus mykiss), leading to high mortality rates. In this study, we systematically engineered three UTR-optimized mRNA constructs, exhibiting comparable and sustained in vitro antigen expression. Following encapsulation, the mG1-LNP formulation, incorporating endogenous antigen-specifics, conferred robust relative protection against IHNV challenge, accompanied by enhanced levels of IgM and neutralizing antibodies. Furthermore, dose-response profiling identified 10 μg/dose as the immunologically optimized regimen, eliciting efficient immunogenicity. Moreover, biodistribution analyses revealed complete mG1-LNP clearance from injection sites and hepatic tissues by 28 dpv, confirming favorable biosafety. Collectively, our work demonstrates the successful development of mRNA-LNP vaccine against infectious IHNV in rainbow trout, providing the first empirical demonstration of mRNA-LNP vaccine efficacy in aquaculture.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"162"},"PeriodicalIF":6.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12284095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691075","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 : 2025-07-22DOI: 10.1038/s41541-025-01225-7
Kwang Hyun Ko, Seung-Hun Baek, Hyun Shik Bae, Young Mi Kim, Sun Hwa Gu, Yu Yeon Jung, Eun Hye Kwak, Han-Gyu Choi, Hwa-Jung Kim, Tae Sun Shim, Dong-Ho Kim, Seung Bin Cha
{"title":"A vaccine targeting lung resident-memory CD4<sup>+</sup> T cell phenotype protects against Mycobacterium tuberculosis in mice.","authors":"Kwang Hyun Ko, Seung-Hun Baek, Hyun Shik Bae, Young Mi Kim, Sun Hwa Gu, Yu Yeon Jung, Eun Hye Kwak, Han-Gyu Choi, Hwa-Jung Kim, Tae Sun Shim, Dong-Ho Kim, Seung Bin Cha","doi":"10.1038/s41541-025-01225-7","DOIUrl":"10.1038/s41541-025-01225-7","url":null,"abstract":"<p><p>Lung-resident memory T (T<sub>RM</sub>) cells respond rapidly and effectively to respiratory pathogen invasion, suppressing pathogen proliferation. Previously, we identified a defined TLR3 agonist called Nexavant (NVT) and developed a vaccine platform that utilizes it to induce lung T<sub>RM</sub>. In this study, we aimed to determine whether the protective effect of T<sub>RM</sub> cells is observed in tuberculosis (TB), a chronic bacterial respiratory disease. We synthesized a peptide vaccine by elongating the CD4<sup>+</sup> T cell epitopes from Mycobacterium tuberculosis antigens ESAT-6, CFP-10, and HspX, adjuvanted it with NVT and administered the vaccine intranasally or intramuscularly to mice. We demonstrated that intranasal administration of an NVT-formulated peptide vaccine induced the generation of CD4<sup>+</sup> T<sub>RM</sub> cells in the lungs, and that our vaccine platform, containing a limited number of CD4 epitopes, provided protective efficacy comparable to that of the BCG vaccine, which contains multiple T cell epitopes. Furthermore, the peptides used in the vaccine were reactive in 23 out of 24 (95.8%) human PBMCs, indicating that they contain promiscuous epitopes. Our results suggest a straightforward approach to controlling pulmonary TB more effectively through the induction of lung CD4<sup>+</sup> T<sub>RM</sub> cells, even when using the same target antigen. Additionally, this study supports a theoretical basis for developing an inhalable TB vaccine using synthetic peptides.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"161"},"PeriodicalIF":6.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12284121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691074","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 : 2025-07-21DOI: 10.1038/s41541-025-01217-7
Bei Liu, Xiyu Zhang, Yongqiang Lai, Tao Sun, Chao Wang, Tianshuo Zhao, Sihui Zhang, Baoguo Shi, Ye Li, Fuqiang Cui
{"title":"Global vaccine confidence trends among adults above and below age 65.","authors":"Bei Liu, Xiyu Zhang, Yongqiang Lai, Tao Sun, Chao Wang, Tianshuo Zhao, Sihui Zhang, Baoguo Shi, Ye Li, Fuqiang Cui","doi":"10.1038/s41541-025-01217-7","DOIUrl":"10.1038/s41541-025-01217-7","url":null,"abstract":"<p><p>This study is interested in global vaccine confidence because it directly impacts vaccination rates and public health outcomes, especially during the COVID-19 pandemic. Furthermore, due to the unique vulnerabilities to vaccine-preventable diseases, misinformation, and access to health information among adults aged 65 and older, understanding vaccine confidence in this population is crucial for developing targeted interventions and improving vaccination rates. The current research is limited by single-country surveys and cross-sectional designs, providing limited insights into these issues. We compared the vaccine confidence between the population over 65 and under 65 in terms of vaccine safety, effectiveness, compatibility with religious beliefs, and importance to children. We employed a hierarchical logistic model, and compared human development index (HDI) values to investigate determinants of vaccine confidence. Vaccine confidence increased between 2015 and 2019, but decreased between 2019 and 2022 across most global regions, exhibiting an inverted U-shaped trend. Population over 65 in high-income countries was more likely to agree on the safety, effectiveness, importance to children, and compatibility of vaccines with religious beliefs than those under 65, with agreement levels exceeding 80% for most aspects. Gender, education, income, and religion influenced vaccine attitudes among adults aged 65 and older. Countries with an HDI exceeding 0.9 consistently demonstrated positive trends in vaccine confidence. This relationship between HDI and vaccine confidence underscores the importance of comprehensive societal development in shaping attitudes toward vaccination. These findings can help develop targeted interventions and policies to improve vaccination rates among older adults.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"160"},"PeriodicalIF":6.9,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12280150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682831","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":"Oncolytic virus-mediated p53 activation boosts the antitumor immunity of a p53-transduced dendritic cell vaccine.","authors":"Motohiko Yamada, Hiroshi Tazawa, Kanto Suemori, Naohiro Okada, Yoshinori Kajiwara, Ryohei Shoji, Yasuo Nagai, Hiroaki Inoue, Naoyuki Hashimoto, Nobuhiko Kanaya, Satoru Kikuchi, Shinji Kuroda, Hiroyuki Michiue, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara","doi":"10.1038/s41541-025-01219-5","DOIUrl":"10.1038/s41541-025-01219-5","url":null,"abstract":"<p><p>Dendritic cells (DCs) transduced with replication-deficient, wild-type human p53-expressing adenovirus Ad-p53 (Ad-p53 DCs) induce p53-targeting cytotoxic T lymphocytes (CTLs). However, the antitumor efficacy of Ad-p53 DCs is diminished by weak p53 immunogenicity in tumor cells and poor immune responses. We developed a p53-armed oncolytic adenovirus, OBP-702, to induce tumor-specific p53 expression and antitumor immune response, suggesting a role for OBP-702 in enhancing the antitumor efficacy of Ad-p53 DCs. The combined effect of Ad-p53 DCs and OBP-702 was investigated using murine colon cancer (CC) tumor models. Ad-p53 DCs were obtained by stimulating bone marrow-derived cells with granulocyte-macrophage colony-stimulating factor, interleukin-4, and Ad-p53. Subcutaneous tumor models of CT26 (p53 wild-type) and MC38 (p53 mutant-type) murine CC cell lines were used to evaluate the therapeutic potential of combination therapy in the terms of tumor growth, abscopal effect, antitumor immune response, and presentation of p53 peptides in tumor cells. Combination therapy with Ad-p53 DCs and OBP-702 significantly suppressed the growth of p53-intact CT26 tumors at treated and untreated sites by inducing tumor-infiltration of CD8+ CTLs and CD11c+ DCs. OBP-702-infected tumor cells presented human p53 epitopes in the context of major histocompatibility complex molecules, which were recognized by CTLs induced by Ad-p53 DCs. Combination therapy significantly suppressed the growth of p53-mutant MC38 tumors by activating the antitumor immune response. Our results suggest that OBP-702-mediated presentation of p53 epitopes on tumor cells enhances the antitumor efficacy of Ad-p53 DCs against murine CC tumors by attracting p53-targeting CTLs.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"158"},"PeriodicalIF":6.9,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668102","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 : 2025-07-19DOI: 10.1038/s41541-025-01198-7
Marwa Alhashimi, Ekramy E Sayedahmed, Ahmed Elkashif, Shubhada K Chothe, Wen-Chien Wang, Muralimanohara S T Murala, Vivek Gairola, Nobuko Wakamatsu, Abhinay Gontu, Santhamani Ramasamy, Lindsey LaBella, Padmaja Jakka, Meera Surendran Nair, Ruth H Nissly, Suresh V Kuchipudi, Suresh K Mittal
{"title":"A multi-antigen-based SARS-CoV-2 vaccine provides higher immune responses and protection against SARS-CoV-2 variants.","authors":"Marwa Alhashimi, Ekramy E Sayedahmed, Ahmed Elkashif, Shubhada K Chothe, Wen-Chien Wang, Muralimanohara S T Murala, Vivek Gairola, Nobuko Wakamatsu, Abhinay Gontu, Santhamani Ramasamy, Lindsey LaBella, Padmaja Jakka, Meera Surendran Nair, Ruth H Nissly, Suresh V Kuchipudi, Suresh K Mittal","doi":"10.1038/s41541-025-01198-7","DOIUrl":"10.1038/s41541-025-01198-7","url":null,"abstract":"<p><p>The emergence of divergent SARS-CoV-2 variants has significantly compromised the effectiveness of first-generation COVID-19 vaccines. We investigated a prime-boost approach using bovine adenoviral (Ad) [BAd] and human Ad (HAd) vectors expressing the spike (S), membrane (M), or nucleocapsid (N) with the autophagy-inducing peptide C5 (AIP-C5) for enhanced antigen-specific immunity. The combinational vaccine formulation expressing three antigens demonstrated markedly elevated antigen-specific cell-mediated immune (CMI) responses compared to groups immunized with vectors expressing individual antigens. Furthermore, vaccinated animals exhibited 100% survival, significant reductions in lung viral titers, and no apparent signs of morbidity following challenges with Delta or Omicron variants in K18-hACE2 transgenic mice. Surprisingly, immunization with vectors expressing M and N resulted in immune suppression. However, including S with M and N overcomes this antagonistic interaction and significantly enhances immune responses and protection efficacy. Using the BAd vaccine platform in a multi-antigen approach complemented with AIP-C5 is a promising strategy for developing next-generation SARS-CoV-2 vaccines.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"159"},"PeriodicalIF":6.9,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668101","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}