Polyvalent mpox mRNA vaccines elicit robust immune responses and confer potent protection against vaccinia virus

• Published in: Cell reports (Cambridge) 2024-06, Vol.43 (6), p.114269, Article 114269
• Main Authors: Ye, Tianxi, Zhou, Jinge, Guo, Chen, Zhang, Kaiyue, Wang, Yuping, Liu, Yanhui, Zhou, Junhui, Xie, Yalin, Li, Entao, Gong, Rui, Zhang, Jiancun, Chuai, Xia, Chiu, Sandra
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Viral - immunology; CP: Immunology; CP: Microbiology; Female; Humans; immune responses; Immunity, Humoral; Mice; Mice, Inbred BALB C; Mpox (monkeypox) - immunology; Mpox (monkeypox) - prevention & control; mpox virus; mRNA vaccine; mRNA Vaccines - immunology; polyvalent vaccine; protection; RNA, Messenger - genetics; RNA, Messenger - immunology; RNA, Messenger - metabolism; Vaccinia - immunology; Vaccinia - prevention & control; Vaccinia virus - genetics; Vaccinia virus - immunology; Viral Vaccines - administration & dosage; Viral Vaccines - immunology
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2024.114269

The 2022 mpox outbreak led the World Health Organization (WHO) to declare it a public health emergency of international concern (PHEIC). There is a need to develop more effective and safer mpox virus (MPXV)-specific vaccines in response to the mpox epidemic. The mRNA vaccine is a promising platform to protect against MPXV infection. In this study, we construct two bivalent MPXV mRNA vaccines, designated LBA (B6R-A29L) and LAM (A35R-M1R), and a quadrivalent mRNA vaccine, LBAAM (B6R-A35R-A29L-M1R). The immunogenicity and protective efficacy of these vaccines alone or in combination were evaluated in a lethal mouse model. All mRNA vaccine candidates could elicit potential antigen-specific humoral and cellular immune responses and provide protection against vaccinia virus (VACV) infection. The protective effect of the combination of two bivalent mRNA vaccines and the quadrivalent vaccine was superior to that of the individual bivalent mRNA vaccine. Our study provides valuable insights for the development of more efficient and safer mRNA vaccines against mpox. [Display omitted] •Multiple MPXV antigens are expressed in one mRNA molecule by a 2A peptide•All polyvalent MPXV mRNA vaccines induce robust immune responses to EEV and IMV antigens•The tetravalent MPXV mRNA vaccines encoding MPXV A35, B6, A29, M1 provide potent protection Ye et al. demonstrate that both the bivalent and tetravalent MPXV mRNA vaccines encoding at least one of EEV and IMV antigens induce robust antigen-specific humoral and cellular immune responses in mice. Furthermore, the two tetravalent vaccines LBAAM and LBA&LAM provide superior protective efficacy against VACV challenge.