title: Adjuvanticity Regulation by Biodegradable Polymeric Nano/microparticle Size.
abstract: Polymeric nano/microparticles as vaccine adjuvants have been researched in experimental and clinical studies. A more profound understanding of how the physicochemical properties regulate specific immune responses has become a vital requirement. Here we prepared poly(d,l-lactic-co-glycolic acid) (PLGA) nano/microparticles with uniform sizes (500 nm, 900 nm, 2.1 μm, and 4.9 μm), and the size effects on particle uptake, activation of macrophages, and antigen internalization were evaluated. Particle uptake kinetic studies demonstrated that 900 nm particles were the easiest to accumulate in cells. Moreover, they could induce macrophages to secrete NO and IL-1β and facilitate antigen internalization. Furthermore, 900 nm particles, mixed with antigen, could exhibit superior adjuvanticity in both humoral and cellular immune responses in vivo, including offering the highest antibody protection, promoting the maximum secretion levels of IFN-γ and IL-4 than particles with other sizes. Overall, 900 nm might be the optimum choice for PLGA particle-based vaccine adjuvants especially for recombinant antigens. Understanding the effect of particle size on the adjuvanticity based immune responses might have important enlightenments for rational vaccine design and applications.
authors.affiliation: State 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.|University of Chinese Academy of Sciences , Beijing 100049, PR China.
authors.forename: Jilei
authors.initials: J
authors.lastname: Jia
authors.affiliation: State 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.|University of Chinese Academy of Sciences , Beijing 100049, PR China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State 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.|University of Chinese Academy of Sciences , Beijing 100049, PR China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: State 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: Tingyuan
authors.initials: T
authors.lastname: Yang
authors.affiliation: State 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: Lianyan
authors.initials: L
authors.lastname: Wang
authors.affiliation: State 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.|Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM) , Nanjing 210023, PR China.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Ma
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000737:chemistry*; D000818:Animals; D000941:Antigens / Q000276:immunology; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D007371:Interferon-gamma / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007700:Kinetics; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D009589:Nitrogen Oxides / Q000378:metabolism; D010316:Particle Size; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry*
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D053583:Interleukin-1beta; D009589:Nitrogen Oxides; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D015847:Interleukin-4; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007371:Interferon-gamma
keywords: PLGA nano/microparticles; adjuvanticity; particle size; vaccine delivery