title: Cationic polypeptide micelle-based antigen delivery system: a simple and robust adjuvant to improve vaccine efficacy.
abstract: Modern subunit vaccines with purified or recombinant antigens are important alternatives to the traditional vaccines. However, there remains a big challenge to elicit potent antibody production and CD8 T cell response. Nanoparticle-based antigen delivery systems have emerged as an innovative strategy to improve the efficacy of subunit vaccines. The present study reported self-assembled cationic micelles based on poly(ethylene glycol)-b-poly(L-lysine)-b-poly(L-leucine) (PEG-PLL-PLLeu) hybrid polypeptides as a simple and potent vaccine delivery system. The results showed that the PEG-PLL-PLLeu micelles spontaneously encapsulated OVA antigens with great loading capacity (LC=55%) and stability. More importantly, the polypeptide micelle formulations robustly enhanced vaccine-induced antibody production by 70-90 fold, which could be due to their capability of inducing dendritic cell maturation, enhancing antigen uptake and presentation, as well as promoting germinal center formation. Furthermore, the polypeptide micelles could simultaneously encapsulate OVA and polyriboinosinic: polyribocytidylic acid (PIC), a TLR3 agonist, to synergistically augment tumor specific cytotoxic-T-lymphocyte (CTL) response. Hence, the polypeptide micelle-based antigen delivery system could be a robust adjuvant to enhance vaccine-induced immune responses.
authors.affiliation: Key Lab of Health Informatics of Chinese Academy of Sciences, Shenzhen, PR China.
authors.forename: Zichao
authors.initials: Z
authors.lastname: Luo
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Jizhe
authors.initials: J
authors.lastname: Deng
authors.forename: Ningning
authors.initials: N
authors.lastname: Gao
authors.forename: Yijuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Pan
authors.forename: Lanlan
authors.initials: L
authors.lastname: Liu
authors.forename: Ce
authors.initials: C
authors.lastname: Wang
authors.forename: Lintao
authors.initials: L
authors.lastname: Cai
authors.forename: Yifan
authors.initials: Y
authors.lastname: Ma
mesh_terms: D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D001854:Bone Marrow Cells / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology; D016503:Drug Delivery Systems; D005260:Female; D018858:Germinal Center / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008823:Micelles; D010047:Ovalbumin / Q000008:administration & dosage*; D010455:Peptides / Q000737:chemistry*; D014612:Vaccines / Q000008:administration & dosage*
chemical_list: D000941:Antigens; D016207:Cytokines; D008823:Micelles; D010455:Peptides; D014612:Vaccines; D010047:Ovalbumin
keywords: Antibody production; Cytotoxic T-lymphocyte response; Dendritic cells; Polypeptide micelles; Vaccine adjuvant