title: Novel vaccine delivery system induces robust humoral and cellular immune responses based on multiple mechanisms.
abstract: Aiming to enhance the immunogenicity of H5N1 split vaccine, the development of a novel antigen delivery system based on quaternized chitosan hydrogel microparticles (Gel MPs) with multiple mechanisms of immunity enhancement is attempted. Gel MPs based on ionic cross-linking are prepared in a simple and mild way. Gel MPs are superior as a vaccine delivery system due to their ability to: 1) enhance cellular uptake and endosomal escape of antigens in dendritic cells (DCs); 2) significantly activate DCs; 3) form an antigen depot and recruit immunity cells to improve antigen capture. Further in vivo investigation shows that Gel MPs, in comparison to aluminum salts (Alum), LPS, and covalent cross-linking quaternized chitosan MPs (GC MPs), induce higher humoral and cellular immune responses with a mixed Th1/Th2 immunity. In conclusion, these results demonstrate that Gel MPs are efficient antigen delivery vehicles based on multiple mechanisms to enhance both humoral and cellular immune responses against H5N1 split antigen.
authors.affiliation: National Key Laboratory of Biochemical Engineering, Key Laboratory of Biopharmaceutical, Production & Formulation Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China.
authors.forename: Yue-Qi
authors.initials: YQ
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.forename: Qing-Ze
authors.initials: QZ
authors.lastname: Fan
authors.forename: Meng
authors.initials: M
authors.lastname: Zhou
authors.forename: Zhan-Guo
authors.initials: ZG
authors.lastname: Yue
authors.forename: Guang-Hui
authors.initials: GH
authors.lastname: Ma
authors.forename: Zhi-Guo
authors.initials: ZG
authors.lastname: Su
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D048271:Chitosan / Q000737:chemistry; D016503:Drug Delivery Systems; D004912:Erythrocytes / Q000473:pathology; D006461:Hemolysis; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology* / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D012756:Sheep
chemical_list: D000914:Antibodies, Viral; D020100:Hydrogels; D007252:Influenza Vaccines; D048271:Chitosan
keywords: H5N1 split vaccines; adjuvants; hydrogels; particulate delivery system; quaternized chitosan