Optimizing vaccine performance through improved cross-presentation with a nanoparticle adjuvant

Abstract

Abstract Activation of CD8 T cells requires presentation of antigenic peptides by MHC I molecules and costimulatory signals provided by CD80 and CD86 on dendritic cells (DCs). Subunit and purified antigen vaccines often fail to induce CD8 T cell responses because the antigens have limited access to the endogenous MHC I pathway, a phenomenon known as antigen cross-presentation. Vaccine adjuvants are being investigated to promote cross-presentation, but adjuvants in currently licensed vaccines are not effective. The goal of this study was to determine if a combination adjuvant (NanoS100) comprised of cationic plant-derived adjuvant nanoparticles (Nano-11) and the synthetic STING agonist ADU-S100 stimulates cross-presentation in vitro and in vivo after intradermal and intranasal vaccination. Incubation of DCs with OVA adsorbed to NanoS100 significantly enhanced the presentation of antigen to the MHC I-restricted OVA-specific B3Z T cell hybridoma compared with OVA only. The cross-presentation was inhibited by preincubation of DCs with chlorpromazine and chloroquine, suggesting that NanoS100 supports endosomal processing of OVA. NanoS100 also significantly increased the expression of CD80 and CD86 on antigen-presenting cells in vitro. Vaccination of mice with OVA and NanoS100 increased humoral and cellular responses with a significant increase of IFNγ+ CD8 T cells in the spleen and the lungs. Intranasal immunization induced a greater percentage of IFNγ+ CD8 T cells in the lungs compared with intradermal immunization. These findings support the potential utility of NanoS100 as a vaccine adjuvant.