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The D3a genotype of CVA6 is the predominant genotype in China. In this study, virus\u2010like particles (VLPs) and mRNA vaccines based on the CVA6 sub\u2010genotype D3a were successfully developed. The immunogenicity and protective effects of the VLP of CVA6 combined with Al(OH)<jats:sub>3<\/jats:sub> and CpG adjuvant indicated that VLP\u2010induced neutralizing antibodies against three CVA6 sub\u2010genotype (D2, D3a, and D3b) strains in Institute of Cancer Research (ICR) mice, and the combination of the two adjuvants enhanced cellular immunity. Passive immunization with serum from mice immunized with VLPs protected suckling mice against CVA6 lethal challenge in both antiserum transfer and maternal immunization experiments. The immunogenicity and protective effects of the mRNA vaccine of CVA6 indicate that it induces robust T\u2010cell immunity. T\u2010cell immunity was found to cross\u2010protect against coxsackievirus A10 infection in mice. This is the first trial of a CVA6 mRNA vaccine worldwide and the first comparison of the immunogenicity and protective effects of VLP and mRNA vaccines based on D3a CVA6. The study provides a theoretical basis for the development of enteroviruses vaccines and the formulation of immunization strategies.<\/jats:p>","DOI":"10.1002\/jmv.70201","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T08:36:36Z","timestamp":1739262996000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Immunogenicity of Coxsackievirus A6 (D3a Sub\u2010Genotype) Virus\u2010Like Particle and mRNA Vaccines"],"prefix":"10.1002","volume":"97","author":[{"given":"Huanhuan","family":"Lu","sequence":"first","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and Prevention No.155, Changbai Road, Changping District Beijing China"},{"name":"National Polio Laboratory, World Health Organization Polio Reference Laboratory 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