C5A Protects Macaques from Vaginal Simian-Human Immunodeficiency Virus Challenge

Antimicrob Agents Chemother. 2015 Nov 9;60(1):693-8. doi: 10.1128/AAC.01925-15. Print 2016 Jan.

Abstract

A safe and effective vaginal microbicide could decrease human immunodeficiency virus (HIV) transmission in women. Here, we evaluated the safety and microbicidal efficacy of a short amphipathic peptide, C5A, in a rhesus macaque model. We found that a vaginal application of C5A protects 89% of the macaques from a simian-human immunodeficiency virus (SHIV-162P3) challenge. We observed no signs of lesions or inflammation in animals vaginally treated with repeated C5A applications. With its noncellular cytotoxic activity and rare mechanism of action, C5A represents an attractive microbicidal candidate.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Intravaginal
  • Amino Acid Sequence
  • Animals
  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / pharmacology*
  • Female
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / immunology
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / immunology
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / immunology
  • Macaca mulatta
  • Models, Molecular
  • Molecular Sequence Data
  • Peptides / chemical synthesis
  • Peptides / pharmacology*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Simian Acquired Immunodeficiency Syndrome / prevention & control*
  • Simian Acquired Immunodeficiency Syndrome / transmission
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / drug effects*
  • Simian Immunodeficiency Virus / physiology
  • Vagina / drug effects*
  • Vagina / immunology
  • Vagina / virology
  • Viral Nonstructural Proteins / antagonists & inhibitors
  • Viral Nonstructural Proteins / chemistry

Substances

  • Anti-HIV Agents
  • Interleukin-2
  • Interleukin-6
  • Interleukin-8
  • Peptides
  • Viral Nonstructural Proteins
  • Interferon-gamma