Herpes simplex virus-2 in the genital mucosa: insights into the mucosal host response and vaccine development

Curr Opin Infect Dis. 2012 Feb;25(1):92-9. doi: 10.1097/QCO.0b013e32834e9a56.


Purpose of review: Herpes simplex virus (HSV)-2 is the predominant cause of genital herpes and has been implicated in HIV infection and transmission. Thus far, vaccines developed against HSV-2 have been clinically ineffective in preventing infection. This review aims to summarize the innate and adaptive immune responses against HSV-2 and examines the current status of vaccine development.

Recent findings: Both innate and adaptive immune responses are essential for an effective primary immune response and the generation of immunity. The innate response involves Toll-like receptors, natural killer cells, plasmacytoid dendritic cells, and type I, II, and III interferons. The adaptive response requires a balance between CD4+ and CD8+ T-cells for optimal viral clearance. T-regulatory cells may be involved, although their exact function has yet to be determined. Current vaccine development involves the use of HSV-2 peptides or attenuated/replication-defective HSV-2 to generate adaptive anti-HSV-2 immune responses, however the generation of innate responses may also be an important consideration.

Summary: Although vaccine development has primarily focused on the adaptive response, arguments for innate involvement are emerging. A greater understanding of the innate and adaptive processes underlying the response to HSV-2 infection will provide the foundation for the development of an effective vaccine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptive Immunity
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Dendritic Cells / immunology
  • Female
  • Genitalia / immunology*
  • Genitalia / virology
  • Herpes Genitalis / drug therapy*
  • Herpes Genitalis / immunology*
  • Herpesvirus 2, Human / immunology*
  • Herpesvirus Vaccines / immunology*
  • Humans
  • Immunity, Innate
  • Interferons / immunology
  • Killer Cells, Natural / immunology
  • Male
  • Mucous Membrane / immunology*
  • Toll-Like Receptors / immunology


  • Herpesvirus Vaccines
  • Toll-Like Receptors
  • Interferons