title: Vectored immunoprophylaxis protects humanized mice from mucosal HIV transmission.
abstract: The vast majority of new HIV infections result from relatively inefficient transmission of the virus across mucosal surfaces during sexual intercourse. A consequence of this inefficiency is that small numbers of transmitted founder viruses initiate most heterosexual infections. This natural bottleneck to transmission has stimulated efforts to develop interventions that are aimed at blocking this step of the infection process. Despite the promise of this strategy, clinical trials of preexposure prophylaxis have had limited degrees of success in humans, in part because of lack of adherence to the recommended preexposure treatment regimens. In contrast, a number of existing vaccines elicit systemic immunity that protects against mucosal infections, such as the vaccines for influenza and human papilloma virus. We recently demonstrated the ability of vectored immunoprophylaxis (VIP) to prevent intravenous transmission of HIV in humanized mice using broadly neutralizing antibodies. Here we demonstrate that VIP is capable of protecting humanized mice from intravenous as well as vaginal challenge with diverse HIV strains despite repeated exposures. Moreover, animals receiving VIP that expresses a modified VRC07 antibody were completely resistant to repetitive intravaginal challenge by a heterosexually transmitted founder HIV strain, suggesting that VIP may be effective in preventing vaginal transmission of HIV between humans.
authors: 1] Division of Biology, California Institute of Technology, Pasadena, California, USA. [2].
authors: Alejandro B
authors: AB
authors: Balazs
authors: Division of Biology, California Institute of Technology, Pasadena, California, USA.
authors: Yong
authors: Y
authors: Ouyang
authors: 1] Division of Biology, California Institute of Technology, Pasadena, California, USA. [2].
authors: Christin M
authors: CM
authors: Hong
authors: Division of Biology, California Institute of Technology, Pasadena, California, USA.
authors: Joyce
authors: J
authors: Chen
authors: Division of Biology, California Institute of Technology, Pasadena, California, USA.
authors: Steven M
authors: SM
authors: Nguyen
authors: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles (UCLA), Los Angeles, California, USA.
authors: Dinesh S
authors: DS
authors: Rao
authors: Department of Translational Sciences, School of Nursing, UCLA AIDS Institute, UCLA, Los Angeles, California, USA.
authors: Dong Sung
authors: DS
authors: An
authors: Division of Biology, California Institute of Technology, Pasadena, California, USA.
authors: David
authors: D
authors: Baltimore
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000737:chemistry; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D000229:Dependovirus / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D057809:HEK293 Cells; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D007114:Immunization / Q000379:methods*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D051379:Mice; D009154:Mutation; D019713:Receptors, CCR5 / Q000378:metabolism; D013997:Time Factors; D014621:Vagina / Q000276:immunology / Q000821:virology*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D019713:Receptors, CCR5; D054299:env Gene Products, Human Immunodeficiency Virus