Xu Qian, Zhang Rong-Rong, Wu Mei, Zhang Jie, Wang Zu-Xin, Chi Hang, Zhou Chao, Xiong Xiao-Chuan, Liu Hai-Tao, Qin Cheng-Feng, Ye Qing
School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing 100071, China.
Vaccines (Basel). 2025 May 13;13(5):514. doi: 10.3390/vaccines13050514.
The re-emerging mpox virus (MPXV) has spread to numerous countries and raised global concern. There is an urgent need for a safe and effective mRNA vaccine candidate against MPXV infection. Previously, we developed a penta-component mRNA vaccine that contained five distinct antigen-encoded mRNAs encapsulated within lipid nanoparticles (LNPs). Here, we sought to develop a single-chain mRNA vaccine that encodes antigens derived from both intracellular mature virion (IMV) and extracellular enveloped virion (EEV). A single-chain mRNA vaccine encoding a fusion protein comprising the ectodomains of M1R (eM1R) and A35R (eA35R) (MPXV) was developed and characterized, while an admixed formulation of two individual mRNA-LNPs encoding separate antigens was developed as the control (MPXV). Meanwhile, based on the same strategy, we designed a single-chain mRNA vaccine encoding dimeric antigens (MPXV). Mice were immunized with two doses of the candidate vaccines, and both humoral and cellular immune responses were evaluated. The protective efficacy of the candidate vaccines was evaluated based on body weight monitoring and tissue viral load measurement after challenge with vaccinia virus (VACV). Immunization with two doses of MPXV elicited robust levels of neutralizing antibodies and antigen-specific cellular immune response. Importantly, MPXV demonstrated protective efficacy in a VACV challenge mouse model and showed superior capacity in preventing weight loss post-challenge compared to MPXV. Similarly, MPXV exhibited comparable or superior immunogenicity and protective efficacy compared to the admixed formulations. The single-chain mRNA vaccine elicited a protective immune response in mice, offering significant advantages in terms of manufacturing processes and quality control. Our single-chain mRNA vaccine platform presents a promising strategy for the next generation design of mpox vaccines and contributes to the mitigation of MPXV endemic worldwide.
再度出现的猴痘病毒（MPXV）已传播至众多国家并引发全球关注。迫切需要一种安全有效的针对MPXV感染的mRNA候选疫苗。此前，我们研发了一种五组分mRNA疫苗，其包含封装在脂质纳米颗粒（LNPs）中的五种不同的抗原编码mRNA。在此，我们试图研发一种编码源自细胞内成熟病毒粒子（IMV）和细胞外被膜病毒粒子（EEV）抗原的单链mRNA疫苗。我们研发并表征了一种编码包含M1R胞外域（eM1R）和A35R胞外域（eA35R）（MPXV）的融合蛋白的单链mRNA疫苗，同时研发了一种编码单独抗原的两种个体mRNA-LNP的混合制剂作为对照（MPXV）。与此同时，基于相同策略，我们设计了一种编码二聚体抗原的单链mRNA疫苗（MPXV）。用两剂候选疫苗对小鼠进行免疫，并评估体液免疫和细胞免疫反应。基于用痘苗病毒（VACV）攻击后的体重监测和组织病毒载量测量来评估候选疫苗的保护效力。用两剂MPXV免疫引发了高水平的中和抗体和抗原特异性细胞免疫反应。重要的是，MPXV在VACV攻击小鼠模型中显示出保护效力，并且与MPXV相比，在预防攻击后体重减轻方面表现出更强的能力。同样，与混合制剂相比，MPXV表现出相当或更强的免疫原性和保护效力。单链mRNA疫苗在小鼠中引发了保护性免疫反应，在制造工艺和质量控制方面具有显著优势。我们的单链mRNA疫苗平台为下一代猴痘疫苗设计提供了一种有前景的策略，并有助于缓解全球范围内的MPXV流行。
