An mRNA vaccine confers enhanced protection against herpes sim-plex virus through a type I interferon-dependent pathway

Herpes simplex virus (HSV) types 1 and 2 cause widespread oral or genital infections, but no prophylactic or therapeutic HSV vaccine has been approved to date. In this study, we developed three mRNA vaccine candidates expressing key viral glycopro-teins: monovalent gD2, bivalent gD2-gC1, and bivalent gD2-gE1. We assessed their immunogenicity and protective efficacy in a murine model. All candidates elicited robust humoral and cellular immunity and provided significant protection against in-travaginal HSV challenge. Notably, the gD2-gE1 vaccine induced markedly stronger immune responses. Mechanistically, its superior immunoprotective efficacy was asso-ciated with the stronger IFN‑I response, which thereby enhanced the adaptive immune response. Collectively, our findings provide a scientific rationale and valuable insights for the future HSV vaccines development