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 language | English (US) |
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Pages (from-to) | 8334-8345 |
Number of pages | 12 |
Journal | Journal of virology |
Volume | 89 |
Issue number | 16 |
DOIs | |
State | Published - Aug 15 2015 |
Bibliographical note
Publisher Copyright:© 2015, American Society for Microbiology.