Dendritic cell-based vaccine treated with polysorbitol transporter enhanced antigen-specific CD8+ T cell immune responses through cross-presentation

Abstract

Abstract Cross-presentation of epitope from exogenous antigen onto MHC I molecule enhances CD8+ T cell activity is important in host protective immune responses against virus infections and cancer. We previously reported that polysorbitol transpoter (PST), prepared from sorbitol diacrylate and low-molecular-weight polyethylenimine, induces a long-term antigen specific B cell response and phagolysosomal escape of antigens in macrophages via mechanism called ‘proton-sponge effect’. Therefore, we hypothesize that PST could enhance the cross-presentation and antigen-specific CD8+ T cell immune responses. In the present study, we tried to determine whether PST could enhance cross-presentation of DC using model antigen Ovalbumin (OVA). PST formed a nano-sized complex with OVA (OVA-PST) enhanced SIINFEKL peptide loading onto MHC I molecules. The results further showed that it enhanced OVA-specific CD8+ T cell proliferation and activation. However, PST was not able to upregulate co-stimulatory molecules and pro-inflammatory cytokines, which are necessary to induce adequate protective immune response. Together with OVA-PST, Monophospholipid A (MPLA), a nontoxic TLR4 agonist which is analog of lipid A also used as co-delivery agent in nanoparticle peptide vaccine, upregulated the effects of OVA-PST complexes. Finally, when PST-OVA and MPLA applied to DC-based vaccine for tumor therapy, survival enhanced in mouse engrafted with tumor. Collectively, these results suggested that the PST enhances cross-presentation in DCs together with antigen-specific CD8+ T cell immune responses. Therefore PST with MPLA could act to improve DC-based vaccine.