Anti-α(4)β(7) monoclonal antibody–conjugated nanoparticles block integrin α(4)β(7) on intravaginal T cells in rhesus macaques

Intravenous administration of anti-α(4)β(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-α(4)β(7) antibody may be safer and more effective. With this in mind, we developed a novel intravaginal formulation consisting of anti-α(4)β(7) monoclonal antibody–conjugated nanoparticles (NPs) loaded in a 1% hydroxyethylcellulose (HEC) gel (NP-α(4)β(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 α(4)β(7), and occupied ~40% of α(4)β(7) expressed by these subsets and ~25% of all cells expressing α(4)β(7). Blocking of the α(4)β(7) was restricted to the vaginal tract without any changes detected systemically.