α-GalCer is an effective mucosal adjuvant for repeated nasal or oral delivery of HIV peptide antigens (39.54)

Abstract

Abstract Mucosal vaccine delivery is important for strong immune responses at biologically relevant sites, however weakly immunogenic antigens delivered by the mucosal route may induce tolerance. Therefore, appropriate adjuvants should be included for effective mucosal immunization. Mice were immunized by the oral or nasal route with alpha-Galactosylceramide (α-GalCer) as an adjuvant for co-administering with a CTL-inducing HIV envelope peptide (R15K). We observed antigen-specific cellular immune responses in multiple systemic and mucosal tissues. Contrary to the known potential of repeated parenteral dosing with α-GalCer to induce NKT cell anergy that could compromise adoptive immunity, we observed that multiple doses delivered by mucosal routes were more efficient in priming broader antigen-specific immune responses. We also obtained results showing that poly-lactic acid based nanoparticles conjugated with α-GalCer can repeatedly stimulate NKT cells both in vitro and in vivo without inducing anergy. Mechanistic studies showed that nanoparticle-formulated α-GalCer is efficiently presented by mouse CD11c+ dendritic cells and CD11b+ macrophages, but very poorly by B220+ B cells. These results demonstrate the effectiveness of α-GalCer as an adjuvant for repeated administration of vaccines for protection against mucosally transmitted pathogens.