Herpes simplex virus-2 Δ gD vaccination primes robust cellular immunity with memory Th17 cell recall following challenge

• Published in: The Journal of immunology (1950) 2016-05, Vol.196 (1_Supplement), p.146-146.3
• Main Authors: Weiss, Kayla A, Petro, Christopher, Herold, Betsy C., Jacobs, William R.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.196.Supp.146.3

Approximately 25 percent of women are infected with herpes simplex virus (HSV)-2 in the United States. Even with anti-viral treatments, the rate of HSV transmission has increased 30 percent in the last 20 years. Furthermore the risk of acquiring an HIV infection increases 2–4 fold for HSV-2-infected individuals. Therefore, the need to have an FDA-approved HSV vaccine is immediate. Recently we have developed a single-cycle HSV-2 vaccine strain genetically deficient in glycoprotein D (HSV-2 ΔgD). Complete protection from disease and the establishment of latency is observed following either HSV-1 or HSV-2 challenge of HSV-ΔgD-vaccinated mice. We have also previously demonstrated that HSV-2 ΔgD elicits a protective, broadly functional antibody response. We hypothesized that HSV-2 ΔgD vaccination also primed T cell immunity, contributing to vaccine-induced protection. We observe both CD4 and CD8 T cells are activated by vaccination, and contract to establish a stable memory population. Vaccine-induced memory CD8 T cells are polyfunctional cytokine-producers with 55 percent specific for the immunodominant HSV gB498-505 epitope. Memory CD4 T cells primed by vaccination are quickly recalled to the infection site following challenge and exhibit a Th17-dominant phenotype with 60 percent of recalled cells producing IL-17A. We also determined that CD4 T cell help is required to stabilize the germinal center B cell population and to elicit protective antibodies following vaccination. Together, our data demonstrate HSV-2 ΔgD vaccination induces robust cellular, as well as humoral, immunity and likely an ideal vaccine vector.