Lu Huanhuan, Xiao Jinbo, Song Jingdong, Song Yang, Li Hai, Ren Hu, Li Jichen, Cong Ruyi, Li Hangwen, Fang Yi, Yan Dongmei, Zhu Shuangli, Sun Qiang, Liu Ying, Zhang Yong
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.
National Polio Laboratory, World Health Organization Polio Reference Laboratory for the Western Pacific Region, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, No.155, Changbai Road, Changping District, Beijing, China.
J Med Virol. 2025 Feb;97(2):e70201. doi: 10.1002/jmv.70201.
In recent years, coxsackievirus A6 (CVA6) has surpassed enterovirus A71 to become the main pathogen causing severe Hand, Foot, and Mouth disease (HFMD) in China with a substantial disease burden. However, there is currently no commercial CVA6 vaccine. The D3a genotype of CVA6 is the predominant genotype in China. In this study, virus-like particles (VLPs) and mRNA vaccines based on the CVA6 sub-genotype D3a were successfully developed. The immunogenicity and protective effects of the VLP of CVA6 combined with Al(OH) and CpG adjuvant indicated that VLP-induced neutralizing antibodies against three CVA6 sub-genotype (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-cell immunity. T-cell immunity was found to cross-protect 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.
近年来，柯萨奇病毒A6（CVA6）已超过肠道病毒A71，成为中国导致重症手足口病（HFMD）的主要病原体，疾病负担沉重。然而，目前尚无商业化的CVA6疫苗。CVA6的D3a基因型是中国的主要基因型。在本研究中，成功开发了基于CVA6 D3a亚型的病毒样颗粒（VLP）和mRNA疫苗。CVA6 VLP与Al(OH)和CpG佐剂联合使用的免疫原性和保护作用表明，VLP可诱导免疫缺陷小鼠（ICR小鼠）产生针对三种CVA6亚型（D2、D3a和D3b）毒株的中和抗体，两种佐剂联合使用可增强细胞免疫。在抗血清转移和母体免疫实验中，用VLP免疫小鼠的血清进行被动免疫可保护乳鼠免受CVA6致死性攻击。CVA6 mRNA疫苗的免疫原性和保护作用表明，它可诱导强大的T细胞免疫。发现T细胞免疫可在小鼠中交叉保护抵抗柯萨奇病毒A10感染。这是全球首次进行CVA6 mRNA疫苗试验，也是首次比较基于CVA6 D3a的VLP和mRNA疫苗的免疫原性和保护作用。该研究为肠道病毒疫苗的开发和免疫策略的制定提供了理论依据。
