title: Improving adjuvanticity of quaternized chitosan-based microgels for H5N1 split vaccine by tailoring the particle properties to achieve antigen dose sparing effect.
abstract: In this study, we developed the quaternized chitosan microgels without chemical crosslinking as an adjuvant of H5N1 split vaccine. The microgels with pH-sensitivity, positive surface charge and good biocompatibility, have been demonstrated in favor of enhancing both humoral and cellular immune response. However, the detailed mechanism of the chitosan-based microgels to enhance antigen specific immune responses remains unclear. Therefore, we prepared the quaternized chitosan microgels with well defined quaternization degrees (QDs, 20-80%) and particle sizes (800nm-5μm) by the premix membrane emulsification technique, and investigated the effect of quaternization degree (QD) and size on the adjuvanticity of microgels. Results suggested that microgels with relatively smaller size (807nm) and moderate quaternization degree (QD 41% and 60%) were favorable for a maximum immune response. The mechanism was studied and explained by examining the characteristics of microgels and investigating the stimulation of bone-marrow derived dendritic cells (BMDCs). Moreover, they induced significantly stronger immune responses at lower antigen doses (known as antigen sparing effect) compared to aluminum adjuvant. These data indicated that a maximum immune response can be achieved by controlling properties of chitosan microgels, which also could serve as a significant guidance for rational design of chitosan-based particle adjuvant.
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Yue-Qi
authors.initials: YQ
authors.lastname: Wang
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Qing-Ze
authors.initials: QZ
authors.lastname: Fan
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yue
authors.affiliation: Hualan Biological Engineering, Inc., Henan, China.
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Ma
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China. Electronic address: wujie@ipe.ac.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China; Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Jiangsu, China. Electronic address: ghma@ipe.ac.cn.
authors.forename: Guang-Hui
authors.initials: GH
authors.lastname: Ma
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China.
authors.forename: Zhi-Guo
authors.initials: ZG
authors.lastname: Su
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000737:chemistry*; D000277:Adjuvants, Pharmaceutic / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D048271:Chitosan / Q000737:chemistry*; D005260:Female; D005782:Gels / Q000008:administration & dosage* / Q000737:chemistry*; D007111:Immunity, Cellular / Q000187:drug effects; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000737:chemistry / Q000276:immunology; D008807:Mice, Inbred BALB C; D010316:Particle Size
chemical_list: D000276:Adjuvants, Immunologic; D000277:Adjuvants, Pharmaceutic; D000914:Antibodies, Viral; D000941:Antigens; D005782:Gels; D007252:Influenza Vaccines; D048271:Chitosan
keywords: Adjuvant; Dose sparing effect; H5N1 split vaccine; Hydrogel; Quaternized chitosan microgels