Induction of mucosal and systemic immune response by single-dose oral immunization with biodegradable microparticles containing DNA encoding HBsAg.
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.
He
Xiao-Wen
XW
Department of Medical Genetics, The Second Military Medical University, No. 800 Xiangyin Road, Yangpu District, 200433 Shanghai, China.
Wang
Fang
F
Department of Medical Genetics, The Second Military Medical University, No. 800 Xiangyin Road, Yangpu District, 200433 Shanghai, China.
Jiang
Lei
L
Department of Medical Genetics, The Second Military Medical University, No. 800 Xiangyin Road, Yangpu District, 200433 Shanghai, China.
Li
Jun
J
Center of New Drug Research, The Naval Medical Research Institution, 200433 Shanghai, China.
Liu
Shan-Kui
SK
School of Pharmaceutical Sciences, The Second Military Medical University, 200433 Shanghai, China.
Xiao
Zhen-Yu
ZY
School of Pharmaceutical Sciences, The Second Military Medical University, 200433 Shanghai, China.
Jin
Xiao-Qin
XQ
Center of New Drug Research, The Naval Medical Research Institution, 200433 Shanghai, China.
Zhang
Ya-Nan
YN
Department of Medical Genetics, The Second Military Medical University, No. 800 Xiangyin Road, Yangpu District, 200433 Shanghai, China.
He
Ying
Y
Department of Medical Genetics, The Second Military Medical University, No. 800 Xiangyin Road, Yangpu District, 200433 Shanghai, China.
Li
Kai
K
Department of Medical Genetics, The Second Military Medical University, No. 800 Xiangyin Road, Yangpu District, 200433 Shanghai, China.
Guo
Ying-Jun
YJ
Department of Medical Genetics, The Second Military Medical University, No. 800 Xiangyin Road, Yangpu District, 200433 Shanghai, China.
Sun
Shu-Han
SH
Department of Medical Genetics, The Second Military Medical University, No. 800 Xiangyin Road, Yangpu District, 200433 Shanghai, China.
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
D017325:Hepatitis B Vaccines; D011108:Polymers; D012367:RNA, Viral; D019444:Vaccines, DNA; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid