title: Intranasal delivery of cationic PLGA nano/microparticles-loaded FMDV DNA vaccine encoding IL-6 elicited protective immunity against FMDV challenge.
abstract: Mucosal vaccination has been demonstrated to be an effective means of eliciting protective immunity against aerosol infections of foot and mouth disease virus (FMDV) and various approaches have been used to improve mucosal response to this pathogen. In this study, cationic PLGA (poly(lactide-co-glycolide)) nano/microparticles were used as an intranasal delivery vehicle as a means administering FMDV DNA vaccine encoding the FMDV capsid protein and the bovine IL-6 gene as a means of enhancing mucosal and systemic immune responses in animals. Three eukaryotic expression plasmids with or without bovine IL-6 gene (pc-P12A3C, pc-IL2AP12A3C and pc-P12AIL3C) were generated. The two latter plasmids were designed with the IL-6 gene located either before or between the P12A and 3C genes, respectively, as a means of determining if the location of the IL-6 gene affected capsid assembly and the subsequent immune response. Guinea pigs and rats were intranasally vaccinated with the respective chitosan-coated PLGA nano/microparticles-loaded FMDV DNA vaccine formulations. Animals immunized with pc-P12AIL3C (followed by animals vaccinated with pc-P12A3C and pc-IL2AP12A3C) developed the highest levels of antigen-specific serum IgG and IgA antibody responses and the highest levels of sIgA (secretory IgA) present in mucosal tissues. However, the highest levels of neutralizing antibodies were generated in pc-IL2AP12A3C-immunized animals (followed by pc-P12AIL3C- and then in pc-P12A3C-immunized animals). pc-IL2AP12A3C-immunized animals also developed stronger cell mediated immune responses (followed by pc-P12AIL3C- and pc-P12A3C-immunized animals) as evidenced by antigen-specific T-cell proliferation and expression levels of IFN-γ by both CD4+ and CD8+ splenic T cells. The percentage of animals protected against FMDV challenge following immunizations with pc-IL2AP12A3C, pc-P12AIL3C or pc-P12A3C were 3/5, 1/5 and 0/5, respectively. These data suggested that intranasal delivery of cationic PLGA nano/microparticles loaded with various FMDV DNA vaccine formulations encoding IL-6 as a molecular adjuvant enhanced protective immunity against FMDV, particularly pc-IL2AP12A3C with IL-6 gene located before P12A3C gene.
authors: State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China.
authors: Gang
authors: G
authors: Wang
authors: Li
authors: L
authors: Pan
authors: Yongguang
authors: Y
authors: Zhang
authors: Yonglu
authors: Y
authors: Wang
authors: Zhongwang
authors: Z
authors: Zhang
authors: Jianliang
authors: J
authors: Lü
authors: Peng
authors: P
authors: Zhou
authors: Yuzhen
authors: Y
authors: Fang
authors: Shoutian
authors: S
authors: Jiang
mesh_terms: D000276:Adjuvants, Immunologic / Q000235:genetics / Q000494:pharmacology; D000281:Administration, Intranasal; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D036022:Capsid Proteins / Q000235:genetics; D002417:Cattle; D048271:Chitosan / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D029544:Foot-and-Mouth Disease Virus / Q000276:immunology*; D006168:Guinea Pigs; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000097:blood; D015850:Interleukin-6 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D019344:Lactic Acid / Q000737:chemistry*; D055616:Microtechnology; D009092:Mucous Membrane / Q000276:immunology; D053758:Nanoparticles / Q000737:chemistry*; D010957:Plasmids / Q000235:genetics; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D059467:Transcriptome / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D036022:Capsid Proteins; D016207:Cytokines; D004337:Drug Carriers; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D015850:Interleukin-6; D019444:Vaccines, DNA; D014765:Viral Vaccines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D048271:Chitosan