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

Erica N. Borducchi, Jinyan Liu, Joseph P. Nkolola, Anthony M. Cadena, Wen-Han Yu, Stephanie Fischinger, Thomas Broge, Peter Abbink, Noe B. Mercado, Abishek Chandrashekar, David Jetton, Lauren Peter, Katherine McMahan, Edward T. Moseley, Elena Bekerman, Joseph Hesselgesser, Wenjun Li, Mark G. Lewis, Galit Alter, Romas Geleziunas and Dan H. Barouch ()
Additional contact information
Erica N. Borducchi: Beth Israel Deaconess Medical Center, Harvard Medical School
Jinyan Liu: Beth Israel Deaconess Medical Center, Harvard Medical School
Joseph P. Nkolola: Beth Israel Deaconess Medical Center, Harvard Medical School
Anthony M. Cadena: Beth Israel Deaconess Medical Center, Harvard Medical School
Wen-Han Yu: Ragon Institute of MGH, MIT, and Harvard
Stephanie Fischinger: Ragon Institute of MGH, MIT, and Harvard
Thomas Broge: Ragon Institute of MGH, MIT, and Harvard
Peter Abbink: Beth Israel Deaconess Medical Center, Harvard Medical School
Noe B. Mercado: Beth Israel Deaconess Medical Center, Harvard Medical School
Abishek Chandrashekar: Beth Israel Deaconess Medical Center, Harvard Medical School
David Jetton: Beth Israel Deaconess Medical Center, Harvard Medical School
Lauren Peter: Beth Israel Deaconess Medical Center, Harvard Medical School
Katherine McMahan: Beth Israel Deaconess Medical Center, Harvard Medical School
Edward T. Moseley: Beth Israel Deaconess Medical Center, Harvard Medical School
Elena Bekerman: Gilead Sciences
Joseph Hesselgesser: Gilead Sciences
Wenjun Li: University of Massachusetts Medical School
Mark G. Lewis: Bioqual
Galit Alter: Ragon Institute of MGH, MIT, and Harvard
Romas Geleziunas: Gilead Sciences
Dan H. Barouch: Beth Israel Deaconess Medical Center, Harvard Medical School

Nature, 2018, vol. 563, issue 7731, 360-364

Abstract: 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.

Keywords: Viral Rebound; TLR7 Agonist; Innate Immune Stimulation; Direct-acting Antivirals; Viral Reservoir (search for similar items in EconPapers)
Date: 2018
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DOI: 10.1038/s41586-018-0600-6

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