title: Immunopotentiator-Loaded Polymeric Microparticles as Robust Adjuvant to Improve Vaccine Efficacy.
abstract: OBJECTIVE
  Adjuvants are required to ensure the efficacy of subunit vaccines. Incorporating molecular immunopotentiators within particles could overcome drawbacks of molecular adjuvants (such as solubility and toxicity), and improve adjuvanticity of particles, achieving stronger adjuvant activity. Aim of this study is to evaluate the adjuvanticity of immunopotentiator-loaded polymeric particles for subunit vaccine.
  
  
  METHODS
  PLGA microparticles (PMPs) and imiquimod (TLR-7 ligand)-loaded PLGA microparticles (IPMPs) were prepared by SPG premix membrane emulsification. In vitro and in vivo studies were performed to their adjuvant activity, using ovalbumin and H5N1 influenza split vaccine as antigens.
  
  
  RESULTS
  Incorporating imiquimod into microparticles significantly improved the efficacy of PLGA microparticles in activating BMDCs and pMΦs, and antigen uptake by pMΦs was also promoted. IPMPs showed stronger adjuvanticity to augment OVA-specific immune responses than PMPs. IgG subclass profiles and cytokine secretion levels by splenocytes indicated that IPMPs elicited more Th1-polarized immune response, compared to PMPs. In vivo study using H5N1 influenza split vaccine as antigen also confirmed the effects of IPMPs on antigen-specific cellular immunity.
  
  
  CONCLUSIONS
  Considering adjuvanticity and safety profiles (PLGA and IMQ, both approved by FDA), we conclude that IMQ-loaded PLGA microparticles are promising robust adjuvant for subunit vaccines.
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, People's Republic of China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Zhang
authors.forename: Lianyan
authors.initials: L
authors.lastname: Wang
authors.forename: Tingyuan
authors.initials: T
authors.lastname: Yang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Chen
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Jilei
authors.initials: J
authors.lastname: Jia
authors.forename: Guanghui
authors.initials: G
authors.lastname: Ma
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry* / Q000494:pharmacology*; D000277:Adjuvants, Pharmaceutic / Q000737:chemistry / Q000494:pharmacology; D000634:Aminoquinolines / Q000737:chemistry / Q000276:immunology; D000818:Animals; D000941:Antigens / Q000276:immunology; D005260:Female; D000077271:Imiquimod; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects / Q000276:immunology; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D014612:Vaccines / Q000737:chemistry / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000277:Adjuvants, Pharmaceutic; D000634:Aminoquinolines; D000941:Antigens; D007074:Immunoglobulin G; D011108:Polymers; D014612:Vaccines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D010047:Ovalbumin; D000077271:Imiquimod