A Single-Chain Mpox mRNA Vaccine Elicits Protective Immune Response in Mice

作者：Qian Xu, Rongrong Zhang, Mei Wu, Jie Zhang, Zu-Xin Wang, Hang Chi, Chao Zhou, Xiao-Chuan Xiong, Haitao Liu, Cheng‐Feng Qin, Qing Ye · 发表于：Vaccines · 年份：2025 · DOI：10.3390/vaccines13050514 · 被引用次数：4 · 研究领域：Poxvirus research and outbreaks、Virus-based gene therapy research、Herpesvirus Infections and Treatments

Background: 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). Methods: A single-chain mRNA vaccine encoding a fusion protein comprising the ectodomains of M1R (eM1R) and A35R (eA35R) (MPXVeM1-eA35) was developed and characterized, while an admixed formulation of two individual mRNA-LNPs encoding separate antigens was developed as the control (MPXVeM1+eA35). Meanwhile, based on the same strategy, we designed a single-chain mRNA vaccine encoding dimeric antigens (MPXVeM1-eA35-Fc). 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). Results: Immunization with two doses of MPXVeM1-eA35 elicited robust levels of neutralizing antibodies and antigen-specific cellular immune response. Importantly, MPXVeM1-eA35 demonstrated protective efficacy in a VACV challenge mouse model and showed...