title: Engineering biomaterial-associated complement activation to improve vaccine efficacy.
abstract: The complement system plays an important role in innate and adaptive immunity, which suggests that complement activation could be exploited as a potential strategy for vaccine adjuvants. Here we explored the potential of chitosan-based microparticles (CS-NH2 MPs) as a vaccine adjuvant with an active surface for complement activation due to the abundance of amino groups. In vaccination studies, using recombinant anthrax protective antigen as a model antigen, compared with the control microparticles (amino-cross-linked MPs), we found that microparticles (MPs) with abundant amino groups significantly enhanced higher antigen-specific IgG titers in vivo and enhanced the production of IL-4 and IFN-γ with ex vivo restimulation. Furthermore, proliferative responses of splenocytes to ex vivo antigen restimulation were enhanced following immunization with MPs with amino groups. Overall, these results indicated that CS-NH2 MPs with a high surface density of amino groups were favorable for complement activation and immune responses. Our data provide further design principles for studies on complement-activating MPs as a vaccine platform.
authors.affiliation: National Key Laboratory of Biochemical Engineering, PLA Key Laboratory of Biopharmaceutical Production & Formulation Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Yin
authors.forename: Lianyan
authors.initials: L
authors.lastname: Wang
authors.forename: Weifeng
authors.initials: W
authors.lastname: Zhang
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Chen
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Yang
authors.forename: Junjie
authors.initials: J
authors.lastname: Xu
authors.forename: Guanghui
authors.initials: G
authors.lastname: Ma
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000881:Anthrax / Q000276:immunology; D000917:Antibody Formation; D049109:Cell Proliferation; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology*; D003167:Complement Activation; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D010316:Particle Size; D013499:Surface Properties; D013601:T-Lymphocytes / Q000502:physiology; D064166:Vaccine Potency
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D048271:Chitosan