Delayed vaginal SHIV infection in VRC01 and anti-α4β7 treated rhesus macaques

VRC01 protects macaques from vaginal SHIV infection after a single high-dose challenge. Infusion of a simianized anti-alpha(4)beta(7) mAb (Rh-alpha(4)beta(7)) just prior to, and during repeated vaginal exposures to SIVmac251 partially protected macaques from vaginal SIV infection and rescued CD4(+) T cells. To investigate the impact of combining VRC01 and Rh-alpha(4)beta(7) on SHIV infection, 3 groups of macaques were treated with a suboptimal dosing of VRC01 alone or in combination with Rh-alpha(4)beta(7) or with control antibodies prior to the initiation of weekly vaginal exposures to a high dose (1000 TCID50) of SHIVAD8-EO. The combination Rh-alpha(4)beta(7)-VRC01 significantly delayed SHIVAD8-EO vaginal infection. Following infection, VRC01-Rh-alpha(4)beta(7)-treated macaques maintained higher CD4(+) T cell counts and exhibited lower rectal SIV-DNA loads compared to controls. Interestingly, VRC01-Rh-alpha(4)beta(7)-treated macaques had fewer IL-17-producing cells in the blood and the gut during the acute phase of infection. Moreover, higher T cell responses to the V2-loop of the SHIVAD8-EO envelope in the VRC01-Rh-alpha(4)beta(7) group inversely correlated with set point viremia. The combination of suboptimal amounts of VRC01 and Rh-alpha(4)beta(7) delayed infection, altered antiviral immune responses and minimized CD4(+) T cell loss. Further exploration of the effect of combining bNAbs with Rh-alpha(4)beta(7) on SIV/HIV infection and antiviral immune responses is warranted and may lead to novel preventive and therapeutic strategies.