Primary oral vaccination followed by a vaginal pull protects mice against genital HSV‐2 infection.

Problem: HSV‐2 infected more than 491 million people aged 15–49 world‐wide in 2016. The morbidity associated with recurrent infections and the increased risk of HIV infection make this a major health problem. To date there is no effective vaccine. Because HSV‐2 ascends to the dorsal route ganglion within 12–18 h of infection, an effective vaccine will need to elicit a strong local resident CD8+ T cell response to prevent the infection from becoming life‐long. Method of Study: Using a mouse model we investigated the potential of oral immunization with a novel lipid adjuvant (LiporaleTM) followed by local vaginal application of an inflammatory agents to protect against primary HSV‐2 infections. Results: Oral vaccination of mice with live‐attenuated HSV‐2 in Liporale followed by vaginal application of DNFB or CXCL9/10 led to recruitment of tissue‐resident CD8+ memory cells into the genital epithelia. This prime and pull vaccination strategy provided complete protection against wild‐type HSV‐2 challenge and prevented viral dissemination to the spinal cords. Conclusions: Activation of mucosal immunity by oral immunization, combined with induction of transient local genital inflammation can recruit long‐lived tissue resident CD8+ T cells into the genital epithelium, providing significant protection against primary HSV‐2 infection. [ABSTRACT FROM AUTHOR]