Journal
JOURNAL OF VIROLOGY
Volume 89, Issue 16, Pages 8334-8345Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.00908-15
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Funding
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH
- NIH Nonhuman Primate Reagent Resource (NIAID) [HHSN 2722000900037C]
- NATIONAL CENTER FOR RESEARCH RESOURCES [R24RR016001] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [ZIAAI005022, ZIAAI005020, K22AI102769] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [DP2DA040254] Funding Source: NIH RePORTER
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Broadly neutralizing antibodies (bnAbs) can prevent lentiviral infection in nonhuman primates and may slow the spread of human immunodeficiency virus type 1 (HIV-1). Although protection by passive transfer of human bnAbs has been demonstrated in monkeys, durable expression is essential for its broader use in humans. Gene-based expression of bnAbs provides a potential solution to this problem, although immune responses to the viral vector or to the antibody may limit its durability and efficacy. Here, we delivered an adeno-associated viral vector encoding a simianized form of a CD4bs bnAb, VRC07, and evaluated its immunogenicity and protective efficacy. The expressed antibody circulated in macaques for 16 weeks at levels up to 66 mu g/ml, although immune suppression with cyclosporine (CsA) was needed to sustain expression. Gene-delivered simian VRC07 protected against simian-human immunodeficiency virus (SHIV) infection in monkeys 5.5 weeks after treatment. Gene transfer of an anti-HIV antibody can therefore protect against infection by viruses that cause AIDS in primates when the host immune responses are controlled. IMPORTANCE Sustained interventions that can prevent HIV-1 infection are needed to halt the spread of the HIV-1 pandemic. The protective capacity of anti-HIV antibody gene therapy has been established in mouse models of HIV-1 infection but has not been established for primates. We show here a proof-of-concept that gene transfer of anti-HIV antibody genes can protect against infection by viruses that cause AIDS in primates when host immune responses are controlled.
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