mRNA Multivalent Antigen Vaccine Strongly Blocks HSV Infection via the IFN‑I Pathway
Critical Limitations and Need for an HSV Vaccine
HSV-1 and HSV-2 infections are common, yet no approved vaccine exists. Previous attempts have been hampered by immune evasion and viral variation.
Design of an mRNA‑Based Multivalent Glycoprotein Vaccine
The research team designed three mRNA vaccines: monovalent gD2, bivalent gD2‑gC1, and bivalent gD2‑gE1. Each encodes a key viral surface protein and is delivered via lipid nanoparticles. They were administered to mice to compare immune responses.
gD2‑gE1 Vaccine Activates the IFN‑I Pathway and Enhances Efficacy
The gD2‑gE1 vaccine elicited the strongest antibody and T‑cell responses, achieving the highest HSV infection blockade rate. Mechanistic analysis revealed that enhanced IFN‑I signaling augments adaptive immunity, indicating that innate immunity substantially boosts vaccine efficacy.
A New Direction for Future HSV Vaccine Development
These results demonstrate that an mRNA vaccine incorporating multiple antigens and modulating IFN‑I can provide robust protection. Scientific evidence has been established to rapidly advance toward clinical trials and human application.
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 glycoproteins: 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 intravaginal HSV challenge. Notably, the gD2-gE1 vaccine induced markedly stronger immune responses. Mechanistically, its superior immunoprotective efficacy was associated 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 development of HSV vaccines.
This study addresses the lack of a vaccine to prevent oral and genital HSV infections, for which no therapeutic options currently exist. Commercialization of a safe and effective mRNA vaccine would markedly reduce the risk of HSV infection in daily life and greatly simplify disease control.