{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T06:19:34Z","timestamp":1787552374285,"version":"build-2736575974"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Multi pathogen vaccines have emerged as a promising strategy to improve vaccine coverage, simplify immunization logistics, and address overlapping global health threats. However, few vaccine platforms have demonstrated robust and durable immune responses against pathogens spanning distinct biological classes. Here, we developed and evaluated a viral-vectored multipathogen vaccine platform based on a heterologous prime\u2013boost regimen combining the highly attenuated vaccinia virus LC16m8\u0394 (m8\u0394) and adeno-associated virus serotype 1 (AAV1). As a preclinical proof-of-concept, antigen-specific immune responses against\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    and SARS-CoV-2 (Omicron variant) were evaluated, while neutralizing activity against mpox virus was assessed to examine the cross-reactive immunity conferred by the vaccinia virus vector. Immunogenicity, protective efficacy, and transmission-blocking activity were evaluated in murine models and mosquito feeding assays. The heterologous m8\u0394 prime\/AAV1 boost regimen induced robust and long-lasting antigen-specific antibody responses that were maintained for up to 32 weeks. Complete sterile protection against transgenic\n                    <jats:italic>Plasmodium berghei<\/jats:italic>\n                    sporozoite challenge was achieved, together with greater than 90% transmission-blocking efficacy in mosquito feeding assays. In parallel, potent neutralizing antibody responses against SARS-CoV-2 Omicron and cross-neutralizing activity against mpox virus were observed. These findings demonstrate the feasibility of the m8\u0394\/AAV1 platform as a versatile viral-vectored multipathogen vaccine platform capable of integrating protozoan and viral antigens, providing a rationale for further preclinical optimization and clinical evaluation of next generation multipathogen vaccines targeting both endemic and emerging infectious diseases.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1812029","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T05:31:10Z","timestamp":1787549470000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A viral-vectored multipathogen vaccine platform based on replication-competent vaccinia virus and adeno-associated virus"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuna","family":"Sato","sequence":"first","affiliation":[{"name":"Laboratory of Vaccinology and Applied Immunology, Kanazawa University School of Pharmacy, Kanazawa","place":["Ishikawa, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaro","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccinology and Applied Immunology, Kanazawa University School of Pharmacy, Kanazawa","place":["Ishikawa, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ammar Abdurrahman","family":"Hasyim","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccinology and Applied Immunology, Kanazawa University School of Pharmacy, Kanazawa","place":["Ishikawa, Japan"]},{"name":"Department of Parasitology, Faculty of Medicine, Universitas Indonesia","place":["Jakarta, Indonesia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Morita","sequence":"additional","affiliation":[{"name":"Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Watashi","sequence":"additional","affiliation":[{"name":"Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccinology and Applied Immunology, Kanazawa University School of Pharmacy, Kanazawa","place":["Ishikawa, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuto","family":"Katayama","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccinology and Applied Immunology, Kanazawa University School of Pharmacy, Kanazawa","place":["Ishikawa, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kartika Hardianti","family":"Zainal","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccinology and Applied Immunology, Kanazawa University School of Pharmacy, Kanazawa","place":["Ishikawa, Japan"]},{"name":"Department of Parasitology, Faculty of Medicine, Universitas Indonesia","place":["Jakarta, Indonesia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuhiro","family":"Iyori","sequence":"additional","affiliation":[{"name":"Research Institute of Pharmaceutical Sciences, Musashino University","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Mizukami","sequence":"additional","affiliation":[{"name":"Division of Gene Therapy, Jichi Medical University, Shimotsuke","place":["Tochigi, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisatoshi","family":"Shida","sequence":"additional","affiliation":[{"name":"Laboratory of Primate Model, Research Center for Infectious Diseases, Institute for Frontier Life and Medical Science, Kyoto University","place":["Kyoto, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeto","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccinology and Applied Immunology, Kanazawa University School of Pharmacy, Kanazawa","place":["Ishikawa, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"B1","volume-title":"World Malaria Report 2023","year":"2023"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00567-2","article-title":"Using cross-species vaccination approaches to counter emerging infectious diseases","volume":"21","author":"Warimwe","year":"2021","journal-title":"Nat Rev Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1186\/s41182-021-00379-z","article-title":"What sub-Saharan African countries can learn from malaria elimination in China","volume":"49","author":"Badmos","year":"2021","journal-title":"Trop Med Health"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.amsu.2022.104366","article-title":"Increasing challenges of malaria control in sub-Saharan Africa: Priorities for public health research and policymakers","volume":"81","author":"Oladipo","year":"2022","journal-title":"Ann Med Surg (Lond)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines10050713","article-title":"Mosquirix Rts, S\/As01 vaccine development, immunogenicity, and efficacy","volume":"10","author":"Nadeem","year":"2022","journal-title":"Vaccines (Basel)"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(22)00273-0","article-title":"Efficacy of Rts,S\/As01(E) malaria vaccine administered according to different full, fractional, and delayed third or early fourth dose regimens in children aged 5-17 months in Ghana and Kenya: An open-label, phase 2b, randomised controlled trial","volume":"22","author":"Samuels","year":"2022","journal-title":"Lancet Infect Dis"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04188-6","article-title":"The emergence, genomic diversity and global spread of Sars-Cov-2","volume":"600","author":"Li","year":"2021","journal-title":"Nature"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-023-00878-2","article-title":"The evolution of sars-cov-2","volume":"21","author":"Markov","year":"2023","journal-title":"Nat Rev Microbiol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2119451","article-title":"Covid-19 vaccine effectiveness against the Omicron (B.1.1.529) variant","volume":"386","author":"Andrews","year":"2022","journal-title":"N Engl J Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02219-5","article-title":"Real-world Covid-19 vaccine effectiveness against the Omicron Ba.2 variant in a Sars-Cov-2 infection-naive population","volume":"29","author":"Lau","year":"2023","journal-title":"Nat Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2206573","article-title":"Covid-19 vaccines - Immunity, variants, boosters","volume":"387","author":"Barouch","year":"2022","journal-title":"N Engl J Med"},{"key":"B12","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/s41392-022-00997-x","article-title":"Sars-Cov-2 Omicron variant: Recent progress and future perspectives","volume":"7","author":"Fan","year":"2022","journal-title":"Signal Transduct Target Ther"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.583077","article-title":"Emerging concepts and technologies in vaccine development","volume":"11","author":"Brisse","year":"2020","journal-title":"Front Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(24)00092-5","article-title":"Facilitating the development of urgently required combination vaccines","volume":"12","author":"Hausdorff","year":"2024","journal-title":"Lancet Glob Health"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00298-16","article-title":"Multivalent and multipathogen viral vector vaccines","volume":"24","author":"Lauer","year":"2017","journal-title":"Clin Vaccine Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00578-z","article-title":"Immunological mechanisms of vaccine-induced protection against Covid-19 in humans","volume":"21","author":"Sadarangani","year":"2021","journal-title":"Nat Rev Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.01526","article-title":"Impact of vaccines; health, economic and social perspectives","volume":"11","author":"Rodrigues","year":"2020","journal-title":"Front Microbiol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2006.03.087","article-title":"Lc16m8: An attenuated smallpox vaccine","volume":"24","author":"Kenner","year":"2006","journal-title":"Vaccine"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines2040755","article-title":"Vaccinia virus Lc16m8\u0394 as a vaccine vector for clinical applications","volume":"2","author":"Kidokoro","year":"2014","journal-title":"Vaccines (Basel)"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0406671102","article-title":"Genetically stable and fully effective smallpox vaccine strain constructed from highly attenuated vaccinia Lc16m8","volume":"102","author":"Kidokoro","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2015.07.076","article-title":"Vaccinia virus strain Lc16m8 defective in the B5r gene keeps strong protection comparable to its parental strain Lister in immunodeficient mice","volume":"33","author":"Yokote","year":"2015","journal-title":"Vaccine"},{"key":"B22","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1186\/s12985-023-02085-0","article-title":"Cross-reactive immune responses to monkeypox virus induced by Mva vaccination in mice","volume":"20","author":"Gao","year":"2023","journal-title":"Virol J"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1005476","article-title":"Sterile protection and transmission blockade by a multistage anti-malarial vaccine in the pre-clinical study","volume":"13","author":"Iyori","year":"2022","journal-title":"Front Immunol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.parint.2022.102652","article-title":"Adeno-associated virus-based malaria booster vaccine following attenuated replication-competent vaccinia virus Lc16m8delta priming","volume":"92","author":"Hasyim","year":"2023","journal-title":"Parasitol Int"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00730","article-title":"Adeno-associated virus as an effective malaria booster vaccine following adenovirus priming","volume":"10","author":"Yusuf","year":"2019","journal-title":"Front Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1372584","article-title":"A two-dose viral-vectored Plasmodium vivax multistage vaccine confers durable protection and transmission-blockade in a pre-clinical study","volume":"15","author":"Yamamoto","year":"2024","journal-title":"Front Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.501122","article-title":"Interleukin-1 and tumor necrosis factor-alpha trigger restriction of hepatitis B virus infection via a cytidine deaminase activation-induced cytidine deaminase (Aid)","volume":"288","author":"Watashi","year":"2013","journal-title":"J Biol Chem"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2022.2122580","article-title":"A replication-competent smallpox vaccine Lc16m8delta-based Covid-19 vaccine","volume":"11","author":"Sakamoto","year":"2022","journal-title":"Emerg Microbes Infect"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.010207-0","article-title":"Virulence and pathophysiology of the Congo Basin and West African strains of monkeypox virus in non-human primates","volume":"90","author":"Saijo","year":"2009","journal-title":"J Gen Virol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1038\/s41541-025-01229-3","article-title":"Malaria bivalent viral vectored vaccine protects against Plasmodium falciparum and vivax and blocks parasite transmission","volume":"10","author":"Yamamoto","year":"2025","journal-title":"NPJ Vaccines"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089","article-title":"Nih Image to Imagej: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat Methods"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0070819","article-title":"Protective efficacy of baculovirus dual expression system vaccine expressing Plasmodium falciparum circumsporozoite protein","volume":"8","author":"Iyori","year":"2013","journal-title":"PloS One"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1800908","article-title":"Baculovirus-induced fast-acting innate immunity kills liver-stage Plasmodium","volume":"201","author":"Emran","year":"2018","journal-title":"J Immunol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"3896","DOI":"10.1038\/s41598-018-21369-y","article-title":"Adenovirus-prime and baculovirus-boost heterologous immunization achieves sterile protection against malaria sporozoite challenge in a murine model","volume":"8","author":"Yoshida","year":"2018","journal-title":"Sci Rep"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3390\/life13030787","article-title":"Evaluating the immunogenicity and safety of a smallpox vaccine to monkeypox in healthy Japanese adults: A single-arm study","volume":"13","author":"Tomita","year":"2023","journal-title":"Life (Basel)"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.jviromet.2016.07.024","article-title":"Species-specific differentiation of variola, monkeypox, and varicella-zoster viruses by multiplex real-time Pcr assay","volume":"236","author":"Maksyutov","year":"2016","journal-title":"J Virol Methods"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03275-y","article-title":"Bnt162b vaccines protect rhesus macaques from Sars-Cov-2","volume":"592","author":"Vogel","year":"2021","journal-title":"Nature"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.202100322","article-title":"Site-specific glycosylation of Sars-Cov-2: Big challenges in mass spectrometry analysis","volume":"22","author":"Campos","year":"2022","journal-title":"Proteomics"},{"key":"B39","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/s41541-022-00503-y","article-title":"The use of viral vectors in vaccine development","volume":"7","author":"Travieso","year":"2022","journal-title":"NPJ Vaccines"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.7883\/yoken.JJID.2016.417","article-title":"A single vaccination of nonhuman primates with highly attenuated smallpox vaccine, Lc16m8, provides long-term protection against monkeypox","volume":"70","author":"Iizuka","year":"2017","journal-title":"Jpn J Infect Dis"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines2030624","article-title":"Developments in viral vector-based vaccines","volume":"2","author":"Ura","year":"2014","journal-title":"Vaccines (Basel)"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines12101155","article-title":"A head-to-head comparative study of the replication-competent vaccinia virus and Aav1-based malaria vaccine versus Rts,S\/As01 in murine models","volume":"12","author":"Zainal","year":"2024","journal-title":"Vaccines (Basel)"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1812029\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T05:31:11Z","timestamp":1787549471000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1812029\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,24]]},"references-count":42,"alternative-id":["10.3389\/fimmu.2026.1812029"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1812029","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,24]]},"article-number":"1812029"}}