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

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