AIDS vaccine: Intranasal immunization using inactivated HIV-1-capturing core-corona type polymeric nanospheres

Abstract

Polymeric nanospheres have been widely used in biomedical applications, such as drug, gene and vaccine delivery systems. Nanospheres with entrapped antigens have recently been shown to possess significant potential as vaccine delivery systems and adjuvants. We previously reported that concanavalin A-immobilized polystyrene nanospheres (Con A-NS) could efficiently capture HIV-1 particles and intranasal immunization with inactivated HIV-1-capturing nanospheres (HIV-NS) induced vaginal anti-HIV-1 IgA antibody responses in mice. In addition, vaginal washes from intranasally immunized mice were capable of neutralizing HIV-1. Moreover, simian/human immunodeficiency virus KU-2-capturing nanospheres (SHIV-NS) immunized macaques exhibited partial protection when vaginally and systemically challenged with pathogenic viruses. HIV-NS is suggested to be particularly suitable to enhance antigen delivery to dendritic cells (DCs). In this study, we investigated the mucosal antibody response in mice after the intravaginal or intranasal immunization in detail with using different sized (360, 660, 940 and 1230 nm) HIV-NS. The amount of immobilized Con A to NS was dependent on the surface area of the particle. Moreover, Con A-NS with different sizes could equally capture inactivated HIV-1. Intravaginal or intranasal immunization by HIV-NS with diameters ranging 360 to 1230 nm significantly induced vaginal antibody responses. However, significant differences on vaginal anti-HIV-1 gp120 IgA and IgG antibodies were not found after intravaginal or intranasal immunization with different sized HIV-NS. These results suggest that HIV-NS provides an efficient vaccine delivery system for the induction of a mucosal immune response and the development of a mucosal vaccine.