Prevention of SHIV transmission by topical IFN-β treatment

R. S. Veazey*, H. A. Pilch-Cooper, TJ Hope, G. Alter, A. M. Carias, M. Sips, X. Wang, B. Rodriguez, S. F. Sieg, A. Reich, P. Wilkinson, M. J. Cameron, M. M. Lederman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Understanding vaginal and rectal HIV transmission and protective cellular and molecular mechanisms is critical for designing new prevention strategies, including those required for an effective vaccine. The determinants of protection against HIV infection are, however, poorly understood. Increasing evidence suggest that innate immune defenses may help protect mucosal surfaces from HIV transmission in highly exposed, uninfected subjects. More recent studies suggest that systemically administered type 1 interferon protects against simian immunodeficiency virus infection of macaques. Here we hypothesized that topically applied type 1 interferons might stimulate vaginal innate responses that could protect against HIV transmission. We therefore applied a recombinant human type 1 interferon (IFN-β) to the vagina of rhesus macaques and vaginally challenged them with pathogenic simian/human immunodeficiency virus (SHIV). Vaginal administration of IFN-β resulted in marked local changes in immune cell phenotype, increasing immune activation and HIV co-receptor expression, yet provided significant protection from SHIV acquisition as interferon response genes were also upregulated. These data suggest that protection from vaginal HIV acquisition may be achieved by activating innate mucosal defenses.

Original languageEnglish (US)
Pages (from-to)1528-1536
Number of pages9
JournalMucosal Immunology
Volume9
Issue number6
DOIs
StatePublished - Nov 1 2016

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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