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Broadly Neutralizing Human Immunodeficiency Virus Type 1 Antibody Gene Transfer Protects Nonhuman Primates from Mucosal Simian-Human Immunodeficiency Virus Infection

Saunders, K.O.; Wang, L.; Joyce, M.G.; Yang, Z.-Y.; Balazs, A.B.; Cheng, C.; Ko, S.-Y.; Kong, W.-P.; Rudicell, R.S.; Georgiev, I.S.; Duan, L.; Foulds, K.E.; Donaldson, M.; Xu, L.; Schmidt, S.D.; Todd, J.-P.; Baltimore, D.; Roederer, M.; Haase, A.T.; Kwong, P.D.; Rao, S.S.; Mascola, J.R.; Nabel, G.J.

Journal of Virology 89(16): 8334-8345

2015


ISSN/ISBN: 1098-5514
PMID: 26041300
DOI: 10.1128/jvi.00908-15
Accession: 057328227

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 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.

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