Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published September 2015 | public
Journal Article Open

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


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.

Additional Information

© 2015 American Society for Microbiology. Received 7 April 2015. Accepted 25 May 2015.. Accepted manuscript posted online 3 June 2015. We thank the members of the Vaccine Research Center Laboratory of Animal Medicine for their technical assistance. We thank Brenda Hartman for her assistance with manuscript preparation. We thank Amarendra Pegu for insightful discussions about the study and manuscript preparation. The macaque control IgG used in these studies was provided by the NIH Nonhuman Primate Reagent Resource (R24 RR016001 and NIAID contract HHSN 2722000900037C). This work was supported by the intramural research program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH. L.W. and M.G.J. contributed equally to the work.

Attached Files

Published - J._Virol.-2015-Saunders-8334-45.pdf


Files (4.0 MB)
Name Size Download all
4.0 MB Preview Download

Additional details

August 20, 2023
August 20, 2023