Broadly neutralizing human immunodeficiency virus type 1 antibody gene transfer protects nonhuman primates from mucosal simianhuman immunodeficiency virus infection

Kevin O. Saunders, Lingshu Wang, M. Gordon Joyce, Zhi Yong Yang, Alejandro B. Balazs, Cheng Cheng, Sung Youl Ko, Wing Pui Kong, Rebecca S. Rudicell, Ivelin S. Georgiev, Lijie Duan, Kathryn E. Foulds, Mitzi Donaldson, Ling Xu, Stephen D. Schmidt, John Paul Todd, David Baltimore, Mario Roederer, Ashley T. Haase, Peter D. KwongSrinivas S. Rao, John R. Mascola, Gary J. Nabel

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)8334-8345
Number of pages12
JournalJournal of virology
Volume89
Issue number16
DOIs
StatePublished - 2015

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