SIV infection, and fail to reconstitute even with optimal antiviral therapy.
Along with the CD4 receptor and CCR5 co-receptor, these cells express integrin α4β7, the gut homing receptor. gp120 binds to α4β7 on T cells and α4β7 defines a T cell subset that is highly susceptible to HIV-1 and SIV infection. These findings suggest that α4β7 could be effective both as an antiviral target and in minimizing trafficking of infected CD4+ T cells into the GALT. To explore that possibility, we developed a primatized rhesus mAb directed against α4β7 that blocks binding to MAdCAM-1.
We evaluated the efficacy of α4β7-mAb therapy in a well characterized NHP model based on repeated, low dose intravaginal challenges with SIVmac251.
We report that i.v. administration of α4β7-mAb markedly reduces surface exposure of α4β7 on CD4+ T cells in the cervico-vaginal canal, significantly delays or prevents trans-vaginal infection, and, when prevention fails, markedly reduces viral DNA loads in the GALT as well as the rate of peripheral CD4+ T cell depletion in SIVmac251-infected macaques. These results suggest that agents directed against α4β7 might be useful for prophylaxis or treatment of HIV infection.