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

TitleAntibody and antiretroviral preexposure prophylaxis prevent cervicovaginal HIV-1 infection in a transgenic mouse model.
Publication TypeJournal Article
Year of Publication2013
AuthorsGruell H, Bournazos S, Ravetch JV, Ploss A, Nussenzweig MC, Pietzsch J
JournalJ Virol
Volume87
Issue15
Pagination8535-44
Date Published08/01/2013
ISSN1098-5514
KeywordsAnimals, Anti-Retroviral Agents, Antigens, CD4, Chemoprevention, Disease Models, Animal, Disease Transmission, Infectious, Female, Genes, Reporter, HIV Antibodies, HIV Infections, Luciferases, Mice, Mice, Inbred C57BL, Mice, Transgenic, Receptors, CCR5
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.

DOI10.1128/JVI.00868-13
Alternate JournalJ. Virol.
PubMed ID23720722
PubMed Central IDPMC3719827
Grant ListAI081677 / AI / NIAID NIH HHS / United States
P01 AI100148 / AI / NIAID NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
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