title: A comparative study of the antigen-specific immune response induced by co-delivery of CpG ODN and antigen using fusion molecules or biodegradable microparticles.
abstract: CpG ODN are toll-like receptor 9 (TLR9) agonists that can enhance antigen presentation by antigen presenting cells (APCs) such as dendritic cells (DCs). The most potent antigen-specific responses are seen when CpG ODN and the antigen are co-localized in the same APC. CpG ODN-antigen fusion molecules and biodegradable microparticles entrapping CpG ODN and antigen can ensure both components are delivered to the same APC. In this study, we compared the efficacy of the CpG-ODN fusion molecules against biodegradable microparticles entrapping antigen and CpG ODN. Microparticles were prepared using a double emulsion solvent evaporation methodology. CpG ODN-OVA fusion molecules were prepared by mixing maleimide-activated protein with thiolated CpG ODN. Both CpG ODN-OVA fusion molecules and microparticles co-entrapping CpG ODN and OVA generated stronger IgG2a and interferon-gamma (IFN-gamma) responses than delivery of soluble CpG ODN and OVA. The microparticles generated stronger IgG2a and IFN-gamma immune responses than did CpG ODN-antigen fusion molecules.
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, University of Iowa, 115 S. Grand Avenue, Iowa City, IA 52242, USA.
authors.forename: Xue-Qing
authors.initials: XQ
authors.lastname: Zhang
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Dahle
authors.forename: George J
authors.initials: GJ
authors.lastname: Weiner
authors.forename: Aliasger K
authors.initials: AK
authors.lastname: Salem
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry; D000534:Alum Compounds; D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D004337:Drug Carriers; D004339:Drug Compounding; D005260:Female; D018796:Immunoconjugates / Q000737:chemistry / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000276:immunology*; D010047:Ovalbumin / Q000737:chemistry / Q000276:immunology*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D013678:Technology, Pharmaceutical / Q000379:methods; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; C408982:CPG-oligonucleotide; C516146:CpG ODN-OVA; D004337:Drug Carriers; D018796:Immunoconjugates; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D011108:Polymers; D011948:Receptors, Antigen, T-Cell; D014614:Vaccines, Synthetic; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C041524:aluminum sulfate; D007371:Interferon-gamma; D010047:Ovalbumin