Blocking α₄β₇ integrin delays viral rebound in SHIV_SF162P3-infected macaques treated with anti-HIV broadly neutralizing antibodies.

Abstract

Anti-HIV broadly neutralizing antibodies (bNAbs) may favor development of antiviral immunity by engaging the immune system during immunotherapy. Targeting integrin α₄β₇ with an anti-α₄β₇ monoclonal antibody (Rh-α₄β₇) affects immune responses in SIV/SHIV-infected macaques. To explore the therapeutic potential of combining bNAbs with α₄β₇ 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-α₄β₇ 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-α₄β₇ 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 α₄β₇ integrin blockade may prolong virologic control by bNAbs in SHIV_SF162P3-infected macaques.