Blocking α4β7 integrin delays viral rebound in SHIVSF162P3-infected macaques treated with anti-HIV broadly neutralizing antibodies

Anti-HIV broadly neutralizing antibodies (bNAbs) may favor development of antiviral immunity by engaging the immune system during immunotherapy. Targeting integrin alpha(4)beta(7) with an anti-alpha(4)beta(7) monoclonal antibody (Rh-alpha(4)beta(7)) affects immune responses in SIV/ SHIV-infected macaques. To explore the therapeutic potential of combining bNAbs with alpha(4)beta(7) integrin blockade, SHIVSF162P3-infected, viremic rhesus macaques were treated with bNAbs only (VRC07-523LS and PGT128 anti-HIV antibodies) or a combination of bNAbs and Rh-alpha(4)beta(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-alpha(4)beta(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 alpha(4)beta(7) integrin blockade may prolong virologic control by bNAbs in SHIVSF162P3-infected macaques.

Automated summary

In this study, it was found that combining bNAbs with Rh-α(4)β(7) integrin blockade delayed viral rebound in SHIVSF162P3-infected macaques compared to treatment with bNAbs alone. The combination therapy showed a modest prolongation of virologic control in some macaques, indicating the potential benefit of targeting both bNAbs and integrin alpha(4)beta(7) in antiviral therapy.