Gender and prior exposure shape innate immune responses to a replication-defective herpes virus vaccine

Here we integrate immune profiling and computational approaches to study responses to a replication-defective herpes simplex virus (HSV) 2 vaccine, in men and women either naive or previously exposed to HSV. Subjects were recipients of a herpes simplex virus (HSV) 2 vaccine in a phase 1 clinical trial where comparisons could be made between three groups of human volunteers based on their HSV serostatus prior to vaccination: HSV1-/HSV2- , HSV1+/HSV2-, or HSV1±/HSV2+ Peripheral blood transcriptomics and cell population frequencies showed the greatest changes on day 1 after vaccination. Prior exposure status and gender were independently associated with responses, but the magnitude of innate responses including type I interferon signatures and TLR7 were greatest in HSV naive women. In contrast, subjects previously infected with HSV had more prominent interferon-I responses. Thus, prior exposure and gender interact to shape innate responses that may also impact adaptive immune phenotypes, such as the neutralizing antibody response which was also faster in HSV naive women than men. Overall design: Gender and prior exposure shape innate immune responses to a replication-defective herpes virus vaccine