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Sci Transl Med. 2017 Sep 20;9(408). pii: eaao4235. doi: 10.1126/scitranslmed.aao4235.

Protection against a mixed SHIV challenge by a broadly neutralizing antibody cocktail.

Author information

1
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
2
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA.
3
Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
4
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
5
The Scripps Research Institute, La Jolla, CA 92037, USA.
6
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA. dbarouch@bidmc.harvard.edu.

Abstract

HIV-1 sequence diversity presents a major challenge for the clinical development of broadly neutralizing antibodies (bNAbs) for both therapy and prevention. Sequence variation in critical bNAb epitopes has been observed in most HIV-1-infected individuals and can lead to viral escape after bNAb monotherapy in humans. We show that viral sequence diversity can limit both the therapeutic and prophylactic efficacy of bNAbs in rhesus monkeys. We first demonstrate that monotherapy with the V3 glycan-dependent antibody 10-1074, but not PGT121, results in rapid selection of preexisting viral variants containing N332/S334 escape mutations and loss of therapeutic efficacy in simian-HIV (SHIV)-SF162P3-infected rhesus monkeys. We then show that the V3 glycan-dependent antibody PGT121 alone and the V2 glycan-dependent antibody PGDM1400 alone both fail to protect against a mixed challenge with SHIV-SF162P3 and SHIV-325c. In contrast, the combination of both bNAbs provides 100% protection against this mixed SHIV challenge. These data reveal that single bNAbs efficiently select resistant viruses from a diverse challenge swarm to establish infection, demonstrating the importance of bNAb cocktails for HIV-1 prevention.

PMID:
28931655
PMCID:
PMC5747528
DOI:
10.1126/scitranslmed.aao4235
[Indexed for MEDLINE]
Free PMC Article

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