Induction of dendritic cell-mediated immune responses against HIV-1 by antigen-capturing nanospheres in mice

Prophylactic vaccines, designed to elicit potent humoral and cellular immune responses to human immunodeficiency virus type 1 (HIV‐1) antigens in mucosa, are the important approach to the protection of individuals against HIV‐1 infection, since HIV‐1 transmission is largely a result of sexual contact. In this study, a novel strategy has been developed to induce HIV‐1‐specific immune responses, which involves inactivated HIV‐1‐caputring concanavalin A (Con A)‐immobilized nanospheres (HIV‐NS) and their interaction with bone marrow (BM)‐derived dendritic cells. HIV‐NS were taken up by dendritic cells via cytoskeleton‐dependent but mannose‐binding site‐independent phagocytosis. Serial stimulations to unprimed T‐cells with HIV‐1 gp120‐capturing NS‐pulsed dendritic cells could induce antigen‐specific T‐cell response. Intranasal administration of fluorescein isothiocyanate‐labeled nanospheres (NS) in mice proved that the particles were taken up into pulmonary dendritic cells. Analysis of mice receiving intranasal immunizations with HIV‐NS revealed that the mice efficiently induced the antibodies against HIV‐1 in the genital tract and specific cytotoxic T‐cells in the spleen. These results suggest that the use of HIV‐1‐NS may provide a novel and promising approach for the induction of humoral and cellular immune responses to HIV‐1. J. Med. Virol. 76:7–15, 2005. © 2005 Wiley‐Liss, Inc.