LAUSR

OBJECTIVE The combined cART and anti-α4β7 RM-Act-1 antibody therapy allows macaques to durably control SIV rebound after withdrawal of the interventions. Here, we aimed to investigate whether vedolizumab (VDZ), a clinical-grade humanized anti-α4β7 antibody, would have similar effects in controlling live HIV-1 infection in humanized mice. DESIGN AND METHODS The integrin α4β7 blockade by VDZ was evaluated on human primary memory CD4 T cells and retinoic acid (RA)-induced gut-homing α4β7 memory CD4 T cells (α4β7MEMT) in vitro. The antiretroviral activity of VDZ was determined using pseudotyped R5-tropic HIV-1SF162, which displays binding activity to α4β7. The preventive and immunotherapeutic efficacies of VDZ were further investigated in humanized mice using the live HIV-1SF162 strain compared with RM-Act-1. RESULTS VDZ effectively and dose-dependently blocked the binding of MAdCAM-1, the native ligand of α4β7, to α4β7MEMT cells. HIV-1SF162 not only displayed binding capacity to α4β7-expressing cells, but also showed an increased infectivity in RA-induced α4β7MEMT cells pre-treated with VDZ. Moreover, VDZ failed to prevent live HIV-1SF162 infection and did not reduce the peak viral load when administrated prior to viral challenge in humanized mice. Lastly, in immunotherapeutic settings, the withdrawal of combined cART with either VDZ or RM-Act-1 resulted in an uncontrolled HIV-1SF162 rebound in humanized mice while the α4β7 molecules remained significantly blocked on circulating CD4 T cells. CONCLUSION VDZ neither prevents nor controls HIV-1SF162 infection both in vitro and in humanized mice. Our findings have significant implications to the clinical application of VDZ in HIV-1 preventive and immunotherapeutic interventions.