Primary Oral or Intramuscular Vaccination Followed by a Vaginal Pull Combine to Reduce Recurrent Genital Pathology in HSV-Infected Guinea Pigs - Abstract
HSV-2 infected over 491 million people in 2016. Reactivation of infection is frequent, causing ulceration of the genital mucosae and viral shedding. Recent studies have suggested that local tissue-resident memory CD8 cells (Trm) are important for protection against HSV infection. Using a guinea pig model, we asked if oral or intramuscular vaccination, followed by transient induction of local inflammation by poly I:C or R848 could protect against recurrent genital pathology in a therapeutic setting. HSV-2 infected female guinea pigs were immunised either orally with live-attenuated HSV-2 in (LiporaleTM) or intramuscularly (IM) with killed HSV-2 in Alum/MPL, either alone or followed by local vaginal application of the inflammatory TLR agonists poly I:C or R848 and monitored for recurrent pathology for 60 days. Both oral immunisation and IM immunisation reduced recurrent pathology in HSV-2-infected guinea pigs. Protection elicited by oral immunisation was further enhanced by vaginal application of both R848 and Poly I:C, while IM immunisation induced protection was only increased by application of R848. Activation of either mucosal or systemic immunity by oral or IM immunisation, combined with induction of transient local genital inflammation provides significant protection against severity of recurrent HSV-2 pathology in guinea pigs.