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T cell immunity to herpes simplex viruses in seronegative subjects: silent infection or acquired immunity?

Abstract
During the course of investigating T cell responses to HSV among volunteers entering trials of investigational genital herpes vaccines, 6 of the 24 immunocompetent subjects with no prior history of oral/labial or genital herpes possessed HSV-specific T cell immunity but, by multiple determinants of even the most sensitive serological assays, remained seronegative to HSV-1 and -2. Of these six immune seronegative (IS; HSV-seronegative with HSV-specific T cell responses) subjects, two had transient HSV-specific T cell responses, while four had CD4(+) and CD8(+) T cell responses directed at HSV that persisted for up to 4 years. CD4(+) T cell clones were isolated that recognized and had high binding affinities to epitopes in HSV-2 tegument proteins. All six IS subjects had potential sexual exposure to an HSV-2-infected sexual partner. Oral and genital mucosal secretions were sampled and tested for the presence of infectious HSV and HSV DNA. No evidence of HSV was detected in >1500 samples obtained from these IS subjects. The identification of persistent T cell responses to HSV in seronegative subjects is a novel finding in the herpesvirus field and suggests either undetected infection or acquired immunity in the absence of infection. Understanding the basis of these acquired immune responses may be critical in developing effective vaccines for genital herpes.
AuthorsChristine M Posavad, Anna Wald, Nancy Hosken, Meei Li Huang, David M Koelle, Rhoda L Ashley, Lawrence Corey
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 170 Issue 8 Pg. 4380-8 (Apr 15 2003) ISSN: 0022-1767 [Print] United States
PMID12682275 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Epitopes, T-Lymphocyte
  • Herpes Simplex Virus Vaccines
Topics
  • Adult
  • CD4-Positive T-Lymphocytes (immunology, virology)
  • CD8-Positive T-Lymphocytes (immunology, virology)
  • Clone Cells
  • Epitopes, T-Lymphocyte (immunology)
  • Female
  • Herpes Genitalis (diagnosis, immunology, virology)
  • Herpes Labialis (diagnosis, immunology, virology)
  • Herpes Simplex (diagnosis, immunology, virology)
  • Herpes Simplex Virus Vaccines (adverse effects, immunology)
  • Herpesvirus 1, Human (immunology, isolation & purification)
  • Herpesvirus 2, Human (immunology, isolation & purification)
  • Humans
  • Immunity, Active (immunology)
  • Immunity, Cellular (immunology)
  • Lymphocyte Activation (immunology)
  • Lymphocyte Count
  • Male
  • T-Lymphocyte Subsets (immunology, virology)
  • T-Lymphocytes, Cytotoxic (immunology, virology)

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