Broadly neutralizing human immunodeficiency virus type 1 antibody gene transfer protects nonhuman primates from mucosal simian-human immunodeficiency virus …

KO Saunders, L Wang, MG Joyce, ZY Yang… - Journal of …, 2015 - Am Soc Microbiol
KO Saunders, L Wang, MG Joyce, ZY Yang, AB Balazs, C Cheng, SY Ko, WP Kong
Journal of virology, 2015Am Soc Microbiol
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 …
Abstract
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 μg/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.
American Society for Microbiology