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

Authors :
Frank I
Cigoli M
Arif MS
Fahlberg MD
Maldonado S
Calenda G
Pegu A
Yang ES
Rawi R
Chuang GY
Geng H
Liu C
Zhou T
Kwong PD
Arthos J
Cicala C
Grasperge BF
Blanchard JL
Gettie A
Fennessey CM
Keele BF
Vaccari M
Hope TJ
Fauci AS
Mascola JR
Martinelli E
Source :
Science translational medicine [Sci Transl Med] 2021 Aug 18; Vol. 13 (607).
Publication Year :
2021

Abstract

Anti-HIV broadly neutralizing antibodies (bNAbs) may favor development of antiviral immunity by engaging the immune system during immunotherapy. Targeting integrin α <subscript>4</subscript> β <subscript>7</subscript> with an anti-α <subscript>4</subscript> β <subscript>7</subscript> monoclonal antibody (Rh-α <subscript>4</subscript> β <subscript>7</subscript> ) affects immune responses in SIV/SHIV-infected macaques. To explore the therapeutic potential of combining bNAbs with α <subscript>4</subscript> β <subscript>7</subscript> integrin blockade, SHIV <subscript>SF162P3</subscript> -infected, viremic rhesus macaques were treated with bNAbs only (VRC07-523LS and PGT128 anti-HIV antibodies) or a combination of bNAbs and Rh-α <subscript>4</subscript> β <subscript>7</subscript> 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 <subscript>4</subscript> β <subscript>7</subscript> 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 <subscript>4</subscript> β <subscript>7</subscript> integrin blockade may prolong virologic control by bNAbs in SHIV <subscript>SF162P3</subscript> -infected macaques.<br /> (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Details

Language :
English
ISSN :
1946-6242
Volume :
13
Issue :
607
Database :
MEDLINE
Journal :
Science translational medicine
Publication Type :
Academic Journal
Accession number :
34408080
Full Text :
https://doi.org/10.1126/scitranslmed.abf7201