Immunogenicity and Protective Efficacy of an mRNA Vaccine Targeting HSV-2 UL41 in Mice

Background: Herpes simplex virus 2 (HSV-2) is the primary cause of sexually transmitted genital ulcerative diseases, for which no effective prophylactic vaccine is currently available. However, the identification of appropriate targets for an HSV-2 mRNA vaccine remains an area requiring further investigation. Methods: The immunogenicity and protective effects of an HSV-2 UL41 mRNA vaccine were evaluated in a BALB/c mouse model. The mice were intramuscularly immunized twice, followed by HSV-2 infection at 28 days post boost. Clinical signs were monitored daily, and the viral load and tissue inflammation were assessed on days 1, 4, and 7 post infection. Dendritic cell (DC) activation in spleen tissue was analyzed via transcriptome sequencing. Results: A comparison of the clinical, immunological, and pathological characteristics of the groups that were immunized with the UL41 mRNA vaccine and then infected with HSV2, along with the control groups, revealed that the vaccine elicited both cellular and humoral immunity, inhibited viral replication, suppressed the inflammatory response, and provided protective effects against the virus in vivo. Furthermore, in vitro assays of DC expansion revealed that the vaccine immunization increased the induction of DCs from splenic cells. Transcriptomic analysis of these DCs revealed the activation of immune signaling pathways. Conclusions: Our study suggests that the UL41 mRNA vaccine may provide effective protection against HSV-2-related diseases and holds promise as a potential mRNA vaccine candidate.