Antibody and Antiretroviral Preexposure Prophylaxis Prevent Cervicovaginal HIV-1 Infection in a Transgenic Mouse Model |
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| Authors: | Henning Gruell Stylianos Bournazos Jeffrey V. Ravetch Alexander Ploss Michel C. Nussenzweig John Pietzsch |
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| Affiliation: | Laboratory of Molecular Immunology,a;Laboratory of Molecular Genetics and Immunology,b;Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease,c The Rockefeller University, New York, New York, USA;Medizinische Fakultät, Westfälische Wilhelms-Universität Münster, Münster, Germanyd;Howard Hughes Medical Institute, ''The Rockefeller University, New York, New York, USAe |
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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. |
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