title: Induction of mucosal and systemic immune response by single-dose oral immunization with biodegradable microparticles containing DNA encoding HBsAg.
abstract: The purpose of this work was to assess the ability of plasmid DNA encoding hepatitis B virus (HBV) HBsAg encapsulated in poly(DL-lactide-co-glycolic acid) (PLGA) microparticles to induce local and systemic HBsAg-specific immunity following a single dose of oral immunization. RT-PCR analysis demonstrated prolonged transcription of plasmid DNA, consistent with the sustained expression and presentation of target antigen observed by confocal laser scanning microscopy, in gut-associated lymphocyte tissue (GALT) from mice immunized orally with plasmid DNA encapsulated into PLGA microparticles. Oral administration of PLGA-DNA microparticles induced a long-lasting and stable antigen-specific antibody response, both serum total antibody and intestinal IgA, in BALB/c mice. Mice immunized orally exhibited antigen-specific gamma interferon production and cytotoxic T lymphocyte responses in spleen and GALT after restimulation in vitro with HBsAg or tumour cells stably expressing HBsAg. In contrast, naked DNA vaccines given by intramuscular injection induced only systemic cellular and humoral responses to HBsAg, which were much lower than the responses elicited by oral DNA encapsulated in PLGA microparticles at equivalent doses. The results are encouraging with regard to obtaining good compliance and vaccination coverage with candidate plasmid DNA vaccines, especially in developing countries.
authors.affiliation: Department of Medical Genetics, The Second Military Medical University, No. 800 Xiangyin Road, Yangpu District, 200433 Shanghai, China.
authors.forename: Xiao-Wen
authors.initials: XW
authors.lastname: He
authors.affiliation: Department of Medical Genetics, The Second Military Medical University, No. 800 Xiangyin Road, Yangpu District, 200433 Shanghai, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Medical Genetics, The Second Military Medical University, No. 800 Xiangyin Road, Yangpu District, 200433 Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Center of New Drug Research, The Naval Medical Research Institution, 200433 Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, The Second Military Medical University, 200433 Shanghai, China.
authors.forename: Shan-Kui
authors.initials: SK
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, The Second Military Medical University, 200433 Shanghai, China.
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Xiao
authors.affiliation: Center of New Drug Research, The Naval Medical Research Institution, 200433 Shanghai, China.
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Jin
authors.affiliation: Department of Medical Genetics, The Second Military Medical University, No. 800 Xiangyin Road, Yangpu District, 200433 Shanghai, China.
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Zhang
authors.affiliation: Department of Medical Genetics, The Second Military Medical University, No. 800 Xiangyin Road, Yangpu District, 200433 Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Medical Genetics, The Second Military Medical University, No. 800 Xiangyin Road, Yangpu District, 200433 Shanghai, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Medical Genetics, The Second Military Medical University, No. 800 Xiangyin Road, Yangpu District, 200433 Shanghai, China.
authors.forename: Ying-Jun
authors.initials: YJ
authors.lastname: Guo
authors.affiliation: Department of Medical Genetics, The Second Military Medical University, No. 800 Xiangyin Road, Yangpu District, 200433 Shanghai, China.
authors.forename: Shu-Han
authors.initials: SH
authors.lastname: Sun
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D018928:Immunity, Mucosal / Q000187:drug effects* / Q000276:immunology; D019344:Lactic Acid / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D017325:Hepatitis B Vaccines; D011108:Polymers; D012367:RNA, Viral; D019444:Vaccines, DNA; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid