Rational development of multicomponent mRNA vaccine candidates against mpox

The re-emerging mpox (formerly monkeypox) virus (MPXV), a member of Orthopoxvirus genus together with variola virus (VARV) and vaccinia virus (VACV), has led to public health emergency of international concern since July 2022. Inspired by the unprecedent success of coronavirus disease 2019 (COVID-19) mRNA vaccines, the development of a safe and effective mRNA vaccine against MPXV is of high priority. Based on our established lipid nanoparticle (LNP)-encapsulated mRNA vaccine platform, we rationally constructed and prepared a panel of multicomponent MPXV vaccine candidates encoding different combinations of viral antigens including M1R, E8L, A29L, A35R, and B6R. In vitro and in vivo characterization demonstrated that two immunizations of all mRNA vaccine candidates elicit a robust antibody response as well as antigen-specific Th1-biased cellular response in mice. Importantly, the penta- and tetra-component vaccine candidates AR-MPXV5 and AR-MPXV4a showed superior capability of inducing neutralizing antibodies as well as of protecting from VACV challenge in mice. Our study provides critical insights to understand the protection mechanism of MPXV infection and direct evidence supporting further clinical development of these multicomponent mRNA vaccine candidates.

Automated summary

The re-emerging mpox virus has become a public health emergency of international concern and developing a safe and effective mRNA vaccine against it is a top priority. Using a lipid nanoparticle-encapsulated mRNA vaccine platform, a panel of multicomponent MPXV vaccine candidates were constructed and prepared, which elicited strong immune responses in mice. Particularly, the penta- and tetra-component vaccine candidates showed superior capability of inducing neutralizing antibodies and protecting mice from VACV challenge. This study provides critical insights for understanding the protection mechanism of MPXV infection and supports further clinical development of these multicomponent mRNA vaccine candidates.