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

Abstract

Intravenous administration of anti-α₄β₇ 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-α₄β₇ antibody may be safer and more effective. With this in mind, we developed a novel intravaginal formulation consisting of anti-α₄β₇ monoclonal antibody-conjugated nanoparticles (NPs) loaded in a 1% hydroxyethylcellulose (HEC) gel (NP-α₄β₇ 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 α₄β₇, and occupied ~40% of α₄β₇ expressed by these subsets and ~25% of all cells expressing α₄β₇ Blocking of the α₄β₇ was restricted to the vaginal tract without any changes detected systemically.