Delivered antigen peptides to resident CD8α DCs in lymph node by micelle-based vaccine augment antigen-specific CD8 effector T cell response.

Although nanoparticle vaccine is one of the promising therapeutic vaccines against cancers and many chronic infections, induction of strong and long-lasting antigen specific T cell response has still remained many challenges. A major challenge in achieving a robust CD8 T cell response is the requirement of spatio-temporal orchestration of antigen cross-presentation in dendritic cells with innate stimulation. CD8α DCs are specialized for cross presentation and critical for cytotoxic T cell responses, which locate in the deeper paracortex of lymph nodes (LNs) in mice. However, due to size exclusion of compartmentalized network in LNs, nanoparticles with a radius of larger than 5 nm are difficult to access to the CD8α DCs. Here, we showed that polyethylene glycol-phosphatidylethanolamine (PEG-PE) micelles had an extensive contact with the resident CD8α DCs in LNs and delivered more OVA peptides than their free form to these DCs. Meanwhile, successfully delivering antigens into the CD8α DCs resulted in the increased cross presentation of antigens and the enhanced generation of effector CD8 T cell. Our findings further demonstrated the critical role of CD8α DCs in cytotoxic T cell immunity in response to PEG-PE micelle-based vaccine, and also provided a valuable approach to generate T cell-mediated immune response.