Journal
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
Volume 147, Issue -, Pages 76-86Publisher
ELSEVIER
DOI: 10.1016/j.ejpb.2019.12.013
Keywords
CD8 alpha(+) DCs; Cytotoxic T cell responses; PEG-PE micelle-based vaccine
Categories
Funding
- Strategic Priority Research Programs of the Chinese Academy of Sciences [XDA09030303]
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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. CD8 alpha(+) 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 CD8 alpha(+) DCs. Here, we showed that polyethylene glycol-phosphatidylethanolamine (PEG-PE) micelles had an extensive contact with the resident CD8 alpha(+) DCs in LNs and delivered more OVA peptides than their free form to these DCs. Meanwhile, successfully delivering antigens into the CD8 alpha(+) 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 CD8 alpha(+) 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.
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