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

Abstract

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 (Liporale^TM ) 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.

Keywords: herpes; oral vaccination; prime and pull; tissue-resident memory.