TLR7 agonist, N6-LS and PGT121 delayed viral rebound in SHIV-infected macaques after antiretroviral therapy interruption
Toll-like receptor 7 (TLR7) agonist and PGT121 (broadly neutralizing antibody, bnAb) administration previously delayed viral rebound and induced SHIV remission. We evaluated the impact of GS-986 (TLR7 agonist) and dual bnAbs on viral rebound after antiretroviral therapy (ART) interruption. Rhesus ma...
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| creator | Hsu, Denise C Schuetz, Alexandra Imerbsin, Rawiwan Silsorn, Decha Pegu, Amarendra Inthawong, Dutsadee Sopanaporn, Jumpol Visudhiphan, Pornsuk Chuenarom, Weerawan Keawboon, Boot Shi, Wei Robb, Merlin L Mascola, John R Geleziunas, Romas Koup, Richard A Barouch, Dan H Michael, Nelson L Vasan, Sandhya |
| description | Toll-like receptor 7 (TLR7) agonist and PGT121 (broadly neutralizing antibody, bnAb) administration previously delayed viral rebound and induced SHIV remission. We evaluated the impact of GS-986 (TLR7 agonist) and dual bnAbs on viral rebound after antiretroviral therapy (ART) interruption. Rhesus macaques inoculated with SHIV-1157ipd3N4 were initiated on daily suppressive ART from Day 14 post SHIV inoculation. Active arm animals (n = 8) received GS-986, N6-LS and PGT121 after plasma viral suppression, starting from week 14. GS-986 induced immune activation and SHIV-specific T cell responses but not viral expression in all the active arm animals. After ART interruption, median time to viral rebound was 6 weeks in the active and 3 weeks in the control arm (p = 0.024). In this animal model, the administration of the combination of GS-986 and dual bnAbs was associated with a modest delay in viral rebound. This strategy should be further evaluated to better understand the underlying mechanisms for the induction of virus-specific immune responses and delay in viral rebound. |
| doi_str_mv | 10.1371/journal.ppat.1009339 |
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We evaluated the impact of GS-986 (TLR7 agonist) and dual bnAbs on viral rebound after antiretroviral therapy (ART) interruption. Rhesus macaques inoculated with SHIV-1157ipd3N4 were initiated on daily suppressive ART from Day 14 post SHIV inoculation. Active arm animals (n = 8) received GS-986, N6-LS and PGT121 after plasma viral suppression, starting from week 14. GS-986 induced immune activation and SHIV-specific T cell responses but not viral expression in all the active arm animals. After ART interruption, median time to viral rebound was 6 weeks in the active and 3 weeks in the control arm (p = 0.024). In this animal model, the administration of the combination of GS-986 and dual bnAbs was associated with a modest delay in viral rebound. This strategy should be further evaluated to better understand the underlying mechanisms for the induction of virus-specific immune responses and delay in viral rebound.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1009339</identifier><identifier>PMID: 33600506</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Agonists ; Animals ; Antibodies ; Antiretroviral agents ; Antiretroviral drugs ; Antiretroviral therapy ; Antiviral activity ; Binding sites ; Biology and life sciences ; CD4 antigen ; Colon ; Colonies ; Colony-stimulating factor ; Cytokines ; Deoxyribonucleic acid ; DNA ; Dosage ; Drug dosages ; Drug therapy ; Glycan ; Granulocyte colony-stimulating factor ; Granulocyte-macrophage colony stimulating factor ; Granulocytes ; HIV ; Human immunodeficiency virus ; Inflammation ; Interferon ; Interleukin 1 ; Interleukin 10 ; Interleukin 12 ; Interleukin 13 ; Interleukin 15 ; Interleukin 18 ; Interleukin 2 ; Interleukin 6 ; Intravenous administration ; Leukocytes (granulocytic) ; Lymph nodes ; Lymphatic system ; Lymphocytes ; Macrophage inflammatory protein ; Medicine and Health Sciences ; Monocytes ; Plasma ; Proteins ; Receptors ; Research and Analysis Methods ; Tumor necrosis factor-TNF</subject><ispartof>PLoS pathogens, 2021-02, Vol.17 (2), p.e1009339-e1009339</ispartof><rights>This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. 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This strategy should be further evaluated to better understand the underlying mechanisms for the induction of virus-specific immune responses and delay in viral rebound.</description><subject>Agonists</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antiretroviral agents</subject><subject>Antiretroviral drugs</subject><subject>Antiretroviral therapy</subject><subject>Antiviral activity</subject><subject>Binding sites</subject><subject>Biology and life sciences</subject><subject>CD4 antigen</subject><subject>Colon</subject><subject>Colonies</subject><subject>Colony-stimulating factor</subject><subject>Cytokines</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Dosage</subject><subject>Drug dosages</subject><subject>Drug therapy</subject><subject>Glycan</subject><subject>Granulocyte colony-stimulating factor</subject><subject>Granulocyte-macrophage colony stimulating 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We evaluated the impact of GS-986 (TLR7 agonist) and dual bnAbs on viral rebound after antiretroviral therapy (ART) interruption. Rhesus macaques inoculated with SHIV-1157ipd3N4 were initiated on daily suppressive ART from Day 14 post SHIV inoculation. Active arm animals (n = 8) received GS-986, N6-LS and PGT121 after plasma viral suppression, starting from week 14. GS-986 induced immune activation and SHIV-specific T cell responses but not viral expression in all the active arm animals. After ART interruption, median time to viral rebound was 6 weeks in the active and 3 weeks in the control arm (p = 0.024). In this animal model, the administration of the combination of GS-986 and dual bnAbs was associated with a modest delay in viral rebound. 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| ispartof | PLoS pathogens, 2021-02, Vol.17 (2), p.e1009339-e1009339 |
| issn | 1553-7374 1553-7366 1553-7374 |
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| source | Public Library of Science (PLoS) Journals Open Access; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; PubMed Central Open Access |
| subjects | Agonists Animals Antibodies Antiretroviral agents Antiretroviral drugs Antiretroviral therapy Antiviral activity Binding sites Biology and life sciences CD4 antigen Colon Colonies Colony-stimulating factor Cytokines Deoxyribonucleic acid DNA Dosage Drug dosages Drug therapy Glycan Granulocyte colony-stimulating factor Granulocyte-macrophage colony stimulating factor Granulocytes HIV Human immunodeficiency virus Inflammation Interferon Interleukin 1 Interleukin 10 Interleukin 12 Interleukin 13 Interleukin 15 Interleukin 18 Interleukin 2 Interleukin 6 Intravenous administration Leukocytes (granulocytic) Lymph nodes Lymphatic system Lymphocytes Macrophage inflammatory protein Medicine and Health Sciences Monocytes Plasma Proteins Receptors Research and Analysis Methods Tumor necrosis factor-TNF |
| title | TLR7 agonist, N6-LS and PGT121 delayed viral rebound in SHIV-infected macaques after antiretroviral therapy interruption |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-28T23%3A28%3A52IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=TLR7%20agonist,%20N6-LS%20and%20PGT121%20delayed%20viral%20rebound%20in%20SHIV-infected%20macaques%20after%20antiretroviral%20therapy%20interruption&rft.jtitle=PLoS%20pathogens&rft.au=Hsu,%20Denise%20C&rft.date=2021-02-01&rft.volume=17&rft.issue=2&rft.spage=e1009339&rft.epage=e1009339&rft.pages=e1009339-e1009339&rft.issn=1553-7374&rft.eissn=1553-7374&rft_id=info:doi/10.1371/journal.ppat.1009339&rft_dat=%3Cproquest_plos_%3E2491952843%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2501884370&rft_id=info:pmid/33600506&rft_doaj_id=oai_doaj_org_article_1bbb3787e2a04da0992cd09014e7ac62&rfr_iscdi=true |