title: Enhanced humoral and cell-mediated immune responses generated by cationic polymer-coated PLA microspheres with adsorbed HBsAg.
abstract: Surface-engineered particulate delivery systems for vaccine administration have been widely investigated in experimental and clinical studies. However, little is known about charge-coated microspheres as potential recombinant subunit protein antigen delivery systems in terms of adsorption and related immune responses. In the present study, cationic polymers, including chitosan (CS), chitosan chloride (CSC), and polyethylenimine (PEI), were used to coat PLA microspheres to build positively charged surfaces. Antigen adsorption capacity was enhanced with increased surface charge of coated microspheres. In macrophages, HBsAg adsorbed on the surface of cationic microspheres specifically enhanced antigen uptake and augmented CD86, MHC I, and MHC II expression and IL-1β, IL-6, TNF-α, and IL-12 release. Antigens were more likely to localize independent of lysosomes after phagocytosis in antigen-attached cationic microsphere formulations. After intraperitoneal immunization, cationic microsphere-based vaccine formulations generated a rapid and efficient humoral immune response and cytokine release as compared with aluminum-adsorbed vaccine and free antigens in vivo. Moreover, microspheres coated with cationic polymers with relatively high positive charges and higher antigen adsorption exhibited strong stimulation of the Th1 response. In conclusion, PLA microspheres coated with cationic polymers may be a potential recombinant antigen delivery system to induce strong cell and humoral immune responses.
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences , Beijing 100190, PR China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Chen
authors.forename: Yuying
authors.initials: Y
authors.lastname: Liu
authors.forename: Lianyan
authors.initials: L
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Weifeng
authors.initials: W
authors.lastname: Zhang
authors.forename: Bei
authors.initials: B
authors.lastname: Fan
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Ma
authors.forename: Qipeng
authors.initials: Q
authors.lastname: Yuan
authors.forename: Guanghui
authors.initials: G
authors.lastname: Ma
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Su
mesh_terms: D000327:Adsorption / Q000276:immunology*; D000818:Animals; D002412:Cations / Q000276:immunology*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000276:immunology; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology*; D056724:Immunity, Humoral / Q000276:immunology*; D007378:Interleukins / Q000276:immunology; D019344:Lactic Acid / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D011091:Polyesters; D011094:Polyethyleneimine / Q000008:administration & dosage; D011108:Polymers / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D002412:Cations; D006514:Hepatitis B Surface Antigens; D007378:Interleukins; D011091:Polyesters; D011108:Polymers; D014409:Tumor Necrosis Factor-alpha; D019344:Lactic Acid; C033616:poly(lactide); D011094:Polyethyleneimine; D048271:Chitosan