Antibody and antiretroviral preexposure prophylaxis prevent cervicovaginal HIV-1 infection in a transgenic mouse model.

  • Gruell H
  • Bournazos S
  • Ravetch J
 et al. 
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Abstract

The development of an effective vaccine preventing HIV-1 infection remains elusive. Thus, the development of novel approaches capable of preventing HIV-1 transmission is of paramount importance. However, this is partly hindered by the lack of an easily accessible small-animal model to rapidly measure viral entry. Here, we report the generation of a human CD4- and human CCR5-expressing transgenic luciferase reporter mouse that facilitates measurement of peritoneal and genitomucosal HIV-1 pseudovirus entry in vivo. We show that antibodies and antiretrovirals mediate preexposure protection in this mouse model and that the serum antibody concentration required for protection from cervicovaginal infection is comparable to that required to protect macaques. Our results suggest that this system represents a model for the preclinical evaluation of prophylactic or vaccine candidates. It further supports the idea that broadly neutralizing antibodies should be evaluated for use as preexposure prophylaxis in clinical trials.

Author-supplied keywords

  • Animals
  • Anti-Retroviral Agents
  • Anti-Retroviral Agents: administration & dosage
  • Antigens, CD4
  • Antigens, CD4: biosynthesis
  • Antigens, CD4: genetics
  • Chemoprevention
  • Chemoprevention: methods
  • Disease Models, Animal
  • Disease Transmission, Infectious
  • Disease Transmission, Infectious: prevention & con
  • Female
  • Genes, Reporter
  • HIV Antibodies
  • HIV Antibodies: administration & dosage
  • HIV Infections
  • HIV Infections: prevention & control
  • Luciferases
  • Luciferases: analysis
  • Luciferases: genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, CCR5
  • Receptors, CCR5: biosynthesis
  • Receptors, CCR5: genetics

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Authors

  • Henning Gruell

  • Stylianos Bournazos

  • Jeffrey V Ravetch

  • Alexander Ploss

  • Michel C Nussenzweig

  • John Pietzsch

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