Augmented humoral and cellular immune responses to hepatitis B DNA vaccine adsorbed onto cationic microparticles.
Plasmid expressing HBV small envelope antigen was formulated with poly(lactide-co-glycolide-acid) (PLGA) and cetyltrimethylammonium bromide (CTAB) to generate highly uniform microparticles. Controlled release of DNA from these microparticles was demonstrated in vitro and in vivo using flow cytometry and confocal laser scanning microscopy with the focus on localization and quantitatively evaluation of antigen-presenting cells (APCs) involved in the expression of target antigen. Compared to mice vaccinated with naked DNA, mice immunized with PLGA-CTAB-DNA microparticles displayed a much higher percentage of CD11c+, HBsAg-expressing APCs in the draining lymph nodes at 24 h and day 14 postinoculation. In addition, a prolonged transcription of plasmid DNA was detected by RT-PCR in mice immunized with the microparticles. A significantly enhanced immunogenicity of PLGA-CTAB-DNA over naked DNA was observed in immunized mice, including higher levels of antibody production, interferon gamma (IFN-gamma) secretion and cytotoxic T lymphocyte activity. Mice immunized with PLGA-CTAB-DNA microparticles also showed greater efficacy of immunoprotection against challenge of transplanted HBsAg-expressing tumor cells. Our data suggest that controlled release of the PLGA-CTAB-DNA microparticles might involve in the mechanisms of its augmented immunogenicity and enhanced immunoprotection.
He
Xiaowen
X
Department of Medical Genetics, The Second Military Medical University, No.800 Xiangyin Road Yangpu district, Shanghai 200433, China.
Jiang
Lei
L
Wang
Fang
F
Xiao
Zhenyu
Z
Li
Jun
J
Liu
Liu Shankui
LS
Li
Dean
D
Ren
Ding
D
Jin
Xiaoqin
X
Li
Kai
K
He
Yin
Y
Shi
Ke
K
Guo
Yingjun
Y
Zhang
Yanan
Y
Sun
Shuhan
S
D000327:Adsorption; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002412:Cations; D000077286:Cetrimonium; D002593:Cetrimonium Compounds; D005079:Excipients; D005260:Female; D005434:Flow Cytometry; D006509:Hepatitis B / Q000517:prevention & control; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000494:pharmacology*; D007111:Immunity, Cellular / Q000187:drug effects*; D007371:Interferon-gamma / Q000096:biosynthesis; D019344:Lactic Acid; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D049329:Nanostructures; D010957:Plasmids / Q000235:genetics; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology
D002412:Cations; D002593:Cetrimonium Compounds; D005079:Excipients; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D011108:Polymers; D012333:RNA, Messenger; D019444:Vaccines, DNA; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007371:Interferon-gamma; D000077286:Cetrimonium