Blocking α 4 β 7 integrin delays viral rebound in SHIV SF162P3 -infected macaques treated with anti-HIV broadly neutralizing antibodies.

Autor: Frank I; Center for Biomedical Research, Population Council, New York, NY, USA., Cigoli M; Center for Biomedical Research, Population Council, New York, NY, USA., Arif MS; Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Fahlberg MD; Tulane National Primate Research Center, Tulane University, Covington, LA, USA., Maldonado S; Center for Biomedical Research, Population Council, New York, NY, USA., Calenda G; Center for Biomedical Research, Population Council, New York, NY, USA., Pegu A; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Yang ES; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Rawi R; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Chuang GY; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Geng H; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Liu C; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Zhou T; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Kwong PD; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Arthos J; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Cicala C; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Grasperge BF; Tulane National Primate Research Center, Tulane University, Covington, LA, USA., Blanchard JL; Tulane National Primate Research Center, Tulane University, Covington, LA, USA., Gettie A; Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY, USA., Fennessey CM; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Keele BF; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Vaccari M; Tulane National Primate Research Center, Tulane University, Covington, LA, USA., Hope TJ; Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Fauci AS; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Mascola JR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA., Martinelli E; Center for Biomedical Research, Population Council, New York, NY, USA. elena.martinelli@northwestern.edu.; Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Jazyk: angličtina
Zdroj: Science translational medicine [Sci Transl Med] 2021 Aug 18; Vol. 13 (607).
DOI: 10.1126/scitranslmed.abf7201
Abstrakt: Anti-HIV broadly neutralizing antibodies (bNAbs) may favor development of antiviral immunity by engaging the immune system during immunotherapy. Targeting integrin α 4 β 7 with an anti-α 4 β 7 monoclonal antibody (Rh-α 4 β 7 ) affects immune responses in SIV/SHIV-infected macaques. To explore the therapeutic potential of combining bNAbs with α 4 β 7 integrin blockade, SHIV SF162P3 -infected, viremic rhesus macaques were treated with bNAbs only (VRC07-523LS and PGT128 anti-HIV antibodies) or a combination of bNAbs and Rh-α 4 β 7 or were left untreated as a control. Treatment with bNAbs alone decreased viremia below 200 copies/ml in all macaques, but seven of eight macaques (87.5%) in the bNAbs-only group rebounded within a median of 3 weeks (95% CI: 2 to 9). In contrast, three of six macaques treated with a combination of Rh-α 4 β 7 and bNAbs (50%) maintained a viremia below 200 copies/ml until the end of the follow-up period; viremia in the other three macaques rebounded within a median of 6 weeks (95% CI: 5 to 11). Thus, there was a modest delay in viral rebound in the macaques treated with the combination antibody therapy compared to bNAbs alone. Our study suggests that α 4 β 7 integrin blockade may prolong virologic control by bNAbs in SHIV SF162P3 -infected macaques.
(Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze: MEDLINE
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