Anti-α4β7 monoclonal antibody-conjugated nanoparticles block integrin α4β7 on intravaginal T cells in rhesus macaques

Intravenous administration of anti-alpha(4)beta(7) monoclonal antibody in macaques decreases simian immunodeficiency virus (SIV) vaginal infection and reduces gut SIV loads. Because of potential side effects of systemic administration, a prophylactic strategy based on mucosal administration of anti-alpha(4)beta(7) antibody may be safer and more effective. With this in mind, we developed a novel intravaginal formulation consisting of anti-alpha(4)beta(7) monoclonal antibody-conjugated nanoparticles (NPs) loaded in a 1% hydroxyethylcellulose (HEC) gel (NP-alpha(4)beta(7) gel). When intravaginally administered as a single dose in a rhesus macaque model, the formulation preferentially bound to CD4(+) or CD3(+) T cells expressing high levels of alpha(4)beta(7), and occupied similar to 40% of alpha(4)beta(7)expressed by these subsets and similar to 25% of all cells expressing alpha(4)beta(7). Blocking of the alpha(4)beta(7) was restricted to the vaginal tract without any changes detected systemically.