Rational mpox vaccine design: immunogenicity and protective effect of individual and multicomponent proteins in mice

作者：Xueting Cheng, Yawei Wang, Baoying Huang, Jialuo Bing, Tangqi Wang, Ruiwen Han, Shuting Huo, Shucai Sun, Li Zhao, Chang Shu, Yao Deng, Wenjie Tan · 发表于：Emerging Microbes & Infections · 年份：2025 · DOI：10.1080/22221751.2025.2482702 · 被引用次数：8 · 研究领域：Poxvirus research and outbreaks、Bacillus and Francisella bacterial research、vaccines and immunoinformatics approaches

The 2022 global mpox virus (MPXV) outbreak highlights the urgent need for safer, next-generation vaccines. We compared the immunogenicity and protective efficacy of individual and multicomponent membrane proteins of MPXV virions in mice to inform the development of a recombinant subunit vaccine against mpox. BALB/c mice were immunized with eukaryotically expressed A35R, A29L, B6R, and M1R proteins, administered individually or in multicomponent combinations with an Al(OH)₃ + CpG oligodeoxynucleotide adjuvant. Three multicomponent protein vaccines (A29/B6, A29/B6/M1, and A29/B6/M1/A35) provided complete protection, but others (individual protein and A35/M1 combinations) provided partial protection against challenge with high-lethal doses of vaccinia virus Western Reserve (VACV-WR). Additionally, A29/B6 conferred partial protection, whereas A29/B6/M1 and A29/B6/M1/A35 provided complete protection against ectromelia virus (ECTV), with A29/B6/M1 being most effective. All vaccines induced strong antigen-specific immunoglobulin G (IgG) and cellular immunity, whereas only four (M1, A35/M1, A29/B6/M1, A29/B6/M1/A35) exhibited significant neutralizing activity against MPXV, VACV-Tiantan, and ECTV. Correlation analysis suggested that neutralizing antibodies and A35-/A29-/B6-specific cellular immunity act as complementary defense mechanisms, potentially providing first- and second-line protection against MPXV and related orthopoxviruses. Collectively, A29/B6/M1 demonstrated the best pro...