Vaccine and Infectious Disease Division

Identifying host immune responses to HSV-2 disease severity

The majority of recurrent genital lesions worldwide are caused by herpes simplex virus type 2 (HSV-2). HSV-2 is a lifelong infection that undergoes periods asymptomatic latency interspersed with episodes of clinical disease, and is associated with an increased risk of HIV acquisition. The race to find an effective vaccine continues. A crucial step in the vaccine development process is to identify markers for vaccine efficacy. Information from these types of studies gives clues as to how to perfect both preventative and post-acquisition treatment.

The objective of this study was to determine if HSV-2 disease severity correlates with peripheral blood circulating CD4+ T-cell and plasmacytoid dendritic cell (pDC) functions. HSV-2-specific CD4+ T-cell responses can be increased by certain vaccines; therefore, a correlation between high CD4+ T cells and low severity would provide a rationale for this type of vaccine. Although pDCs are part of the innate immune system that does not typically have immune memory, some modern vaccine formats can also stimulate these rare cells. A team of VIDD scientists including associate member Dr. Amalia Magaret, former physician Dr. Karen Mark (now interim chief of the Office of AIDS, California Department of Public Health), assistant member Dr. Josh Schiffer, member Dr. Anna Wald and affiliate investigator Dr. David Koelle collected blood samples and genital swabs from a cohort of individuals at the UW Virology Research Clinic in collaboration with VIDD. HSV-2 disease severity is determined by the frequency of viral shedding and/or lesion formation. Circulating CD4+ T-cell antiviral responses, measured via production of antiviral cytokines IFNγ, IL-2 and TNFα, were not associated with herpes severity. pDC cell numbers from study subjects did not correlate with herpes shedding or lesion rate. Similarly, pDC innate responses to whole HSV-2, specifically IFNα and TNFα, did not correlate with herpes severity. These results stress the importance of measuring not just circulating CD4+ T cells and pDCs for correlative studies of HSV-2 disease severity, but also examining immune responses of other cell types, such as CD8+ T cells or NK cells, either in the blood or localized to sites of infection. These data become especially crucial when evaluating the effect of potential herpes vaccines on HSV-2 pathogenesis.  – MDM

Moss NJ, Magaret A, Laing KJ, Kask AS, Wang M, Mark KE, Schiffer JT, Wald A, Koelle DM. Peripheral blood CD4 T-cell and plasmacytoid dendritic cell (pDC) reactivity to herpes simplex virus 2 and pDC number do not correlate with the clinical or virologic severity of recurrent genital herpes. J Virol. 2012 Sep;86(18):9952-63.