Antibody-mediated protection against genital herpes simplex virus type 2 disease in mice by Fc gamma receptor-dependent and -independent mechanisms

Chin Fun Chu, Michael G. Meador, Christal G. Young, Jane E. Strasser, Nigel Bourne, Gregg N. Milligan

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

The ability of antibody (Ab) to modulate HSV pathogenesis is well recognized but the mechanisms by which HSV-specific IgG antibodies protect against genital HSV-2 disease are not well understood. The requirement for Ab interactions with Fcγ receptors (FcγR) in protection was examined using a murine model of genital HSV-2 infection. IgG antibodies isolated from the serum of HSV-immune mice protected normal mice against HSV-2 disease when administered prior to genital HSV-2 inoculation. However, protection was significantly diminished in recipient mice lacking the gamma chain subunit utilized in FcγRI, FcγRIII, FcγRIV and FcepsilonRI receptors and in normal mice depleted of Gr-1+ immune cell populations known to express FcγR, suggesting protection was largely mediated by an FcγR-dependent mechanism. To test whether neutralizing Ab might provide superior protection, a highly neutralizing HSV glycoprotein D (gD)-specific monoclonal antibody (mAb) was utilized. Similar to results with HSV-specific polyclonal IgG, administration of the gD-specific mAb did not prevent initial infection of the genital tract but resulted in lower virus loads in the vaginal epithelium and provided significant protection against disease and acute infection of the sensory ganglia; however, this protection was independent of host FcγR expression and was manifest in mice depleted of Gr-1+ immune cells. Together, these data demonstrate that substantial Ab-mediated protection against genital HSV-2 disease could be achieved by either FcγR-dependent or -independent mechanisms. These studies suggest that HSV vaccines might need to elicit multiple, diverse antibody effector mechanisms to achieve optimal protection.

Original languageEnglish (US)
Pages (from-to)58-67
Number of pages10
JournalJournal of Reproductive Immunology
Volume78
Issue number1
DOIs
StatePublished - Jun 2008

Keywords

  • Antibodies
  • Fc gamma receptors
  • Genital mucosa
  • Herpes simplex virus type 2
  • Sensory neurons

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynecology

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