Vaccine and Infectious Disease Division

A test for the T cell immune response to HSV-2

Herpesviruses are known for causing recurrent clinical episodes, usually in the form of a sore on the skin or genital surfaces. HSV-2, the virus that causes most episodes of recurrent genital herpes, is prevalent worldwide, with rates ranging from 17% (in the US) to 95% (in some HIV-infected persons and female sex-workers). In recent years, it has become evident that HSV-2 infection elevates the risk of HIV acquisition, a fact that has brought this pathogen to the forefront of therapeutic and vaccination research programs. Until recently, vaccines for HSV-2 have stimulated the arm of the host immune system that leads to antibody production. The last decade has brought discoveries that the second immune system arm, cell mediated immunity, plays a large role in virus recognition and containment. Now, researchers are focusing on developing HSV-2 vaccines that also stimulate this second arm, which is comprised of both CD4 T cells and CD8 T cells. To evaluate the efficacy of these candidate vaccines, scientists must be able to test the strength of the immune response they elicit.

To address this issue, researchers at the Hutchinson Center and the University of Washington, including VIDD affiliate staff scientist Dr. Christine Posavad and colleagues, set out to develop a rapid, quantitative assay that will measure the T cell response to HSV-2 infection. Eighty-one subjects from the Seattle area were enrolled in the study. This cohort consisted of 3 groups: 1) HSV negative; 2) HSV-1 positive but HSV-2 negative; and 3) HSV-2 positive. Blood samples containing peripheral blood mononuclear cells (PBMC), which include T cells, were taken from each subject and then exposed to various HSV-2 protein fragments, also known as antigens or peptides. The test indicated the magnitude of T cell responses to peptides by measuring IFN-γ levels, a molecule produced by activated T cells. The results showed that 85 percent of HSV-2 positive subjects had a positive response to at least one of the peptide fractions, compared to 40 percent for HSV-1 positive and 6 percent for HSV negative subjects. The antigen most frequently recognized was gD-2, an HSV-2 envelope glycoprotein, which is consistent with previous findings. This assay will be valuable for future HSV-2 candidate vaccine studies.

Posavad CM, Magaret AM, Zhao L, Mueller DE, Wald A, and Corey L.  Development of an interferon-gamma ELISPOT assay to detect human T cell responses to HSV-2.  Vaccine 2011 Jul 27.