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Nature. 2018 Nov;563(7731):360-364. doi: 10.1038/s41586-018-0600-6. Epub 2018 Oct 3.

Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys.

Author information

1
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
2
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
3
Gilead Sciences, Foster City, CA, USA.
4
University of Massachusetts Medical School, Worcester, MA, USA.
5
Bioqual, Rockville, MD, USA.
6
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. dbarouch@bidmc.harvard.edu.
7
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA. dbarouch@bidmc.harvard.edu.

Abstract

The latent viral reservoir is the critical barrier for the development of a cure for HIV-1 infection. Previous studies have shown direct antiviral activity of potent HIV-1 Env-specific broadly neutralizing antibodies (bNAbs) administered when antiretroviral therapy (ART) was discontinued, but it remains unclear whether bNAbs can target the viral reservoir during ART. Here we show that administration of the V3 glycan-dependent bNAb PGT121 together with the Toll-like receptor 7 (TLR7) agonist vesatolimod (GS-9620) during ART delayed viral rebound following discontinuation of ART in simian-human immunodeficiency virus (SHIV)-SF162P3-infected rhesus monkeys in which ART was initiated during early acute infection. Moreover, in the subset of monkeys that were treated with both PGT121 and GS-9620 and that did not show viral rebound after discontinuation of ART, adoptive transfer studies and CD8-depletion studies also did not reveal virus. These data demonstrate the potential of bNAb administration together with innate immune stimulation as a possible strategy for targeting the viral reservoir.

PMID:
30283138
PMCID:
PMC6237629
[Available on 2019-04-03]
DOI:
10.1038/s41586-018-0600-6

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