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

Nature (London), 2018-11, Vol.563 (7731), p.360-364 [Peer Reviewed Journal]

COPYRIGHT 2018 Nature Publishing Group ;COPYRIGHT 2018 Nature Publishing Group ;Copyright Nature Publishing Group Nov 15, 2018 ;ISSN: 0028-0836 ;EISSN: 1476-4687 ;DOI: 10.1038/s41586-018-0600-6 ;PMID: 30283138

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Title:
Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys
Author: Borducchi, Erica N ; Liu, Jinyan ; Nkolola, Joseph P ; Cadena, Anthony M ; Yu, Wen-Han ; Fischinger, Stephanie ; Broge, Thomas ; Abbink, Peter ; Mercado, Noe B ; Chandrashekar, Abishek ; Jetton, David ; Peter, Lauren ; McMahan, Katherine ; Moseley, Edward T ; Bekerman, Elena ; Hesselgesser, Joseph ; Li, Wenjun ; Lewis, Mark G ; Alter, Galit ; Geleziunas, Romas ; Barouch, Dan H
Subjects: Adoptive Transfer ; Animals ; Anti-HIV Agents - administration & dosage ; Anti-HIV Agents - therapeutic use ; Antibodies ; Antibodies, Neutralizing - immunology ; Antibodies, Viral - immunology ; Antiretroviral agents ; Antiretroviral drugs ; Antiretroviral therapy ; Antiviral activity ; Antiviral agents ; Binding sites ; Biological products ; CD8 antigen ; CD8 Antigens - deficiency ; CD8 Antigens - immunology ; Deoxyribonucleic acid ; Depletion ; DNA ; DNA, Viral - analysis ; Dosage and administration ; Drug therapy ; Female ; Glycan ; Health aspects ; Highly active antiretroviral therapy ; HIV ; HIV Antibodies - immunology ; HIV infection ; HIV infections ; HIV-1 - drug effects ; HIV-1 - genetics ; HIV-1 - immunology ; Human immunodeficiency virus ; Humans ; Immune system ; Immunity, Cellular - drug effects ; Immunity, Cellular - immunology ; Immunity, Innate - drug effects ; Immunity, Innate - immunology ; Immunoglobulins ; Infection ; Infections ; Lymphatic system ; Macaca mulatta - immunology ; Macaca mulatta - virology ; Male ; Medical research ; Monkeys ; Proteins ; Pteridines - pharmacology ; Simian Acquired Immunodeficiency Syndrome - drug therapy ; Simian Acquired Immunodeficiency Syndrome - immunology ; Simian Acquired Immunodeficiency Syndrome - therapy ; Simian Immunodeficiency Virus - drug effects ; Simian Immunodeficiency Virus - genetics ; Simian Immunodeficiency Virus - immunology ; TLR7 protein ; Toll-Like Receptor 7 - agonists ; Toll-Like Receptor 7 - immunology ; Toll-like receptors ; Viral antibodies ; Viral Load ; Viruses
Is Part Of: Nature (London), 2018-11, Vol.563 (7731), p.360-364
Description: 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.
Publisher: England: Nature Publishing Group
Language: English
Identifier: ISSN: 0028-0836
EISSN: 1476-4687
DOI: 10.1038/s41586-018-0600-6
PMID: 30283138
Source: ProQuest One Psychology
MEDLINE
ProQuest Central

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

COPYRIGHT 2018 Nature Publishing Group ;COPYRIGHT 2018 Nature Publishing Group ;Copyright Nature Publishing Group Nov 15, 2018 ;ISSN: 0028-0836 ;EISSN: 1476-4687 ;DOI: 10.1038/s41586-018-0600-6 ;PMID: 30283138

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