Enhanced antigen-specific antibody production following polyplex-based DNA vaccination via the intradermal route in mice.
DNA vaccination is an attractive approach with various advantages over conventional vaccination. The present study was undertaken to examine whether polyplex-based DNA vaccination could be used to modulate immune responses by plasmid DNA (pDNA). Methylated bovine serum albumin (mBSA) was used as a model of a cationic macromolecular carrier of pDNA encoding obalbumin (OVA) and the effects of polyplex formation of pDNA with mBSA on the antigen-specific immune responses were examined. Anti-OVA IgG antibody production was significantly increased following intradermal immunization with the polyplex compared with naked pDNA, although the induction of cytotoxic T lymphocyte activity was lowered by polyplex formation. We also demonstrated that the disposition and gene expression of pDNA following intradermal injection could be manipulated by polyplex formation. Intriguingly, we also found that the migration of dendritic cells to the injected site could be induced by polyplex formation probably due to a high level of tumor necrosis factor alpha production from the keratinocytes treated with mBSA/pDNA complexeses. Thus, the present study has demonstrated that the immune responses could be biased towards a Th2-type response by polyplex-based DNA vaccination through manipulation of not only pDNA disposition but also dendritic cell migration.
Kawase
Atsushi
A
Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Isaji
Keiko
K
Yamaoka
Ayumi
A
Kobayashi
Naoki
N
Nishikawa
Makiya
M
Takakura
Yoshinobu
Y
D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D039521:CD11c Antigen / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D017930:Genes, Reporter; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007271:Injections, Intradermal; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology*; D010957:Plasmids / Q000235:genetics; D012710:Serum Albumin, Bovine / Q000008:administration & dosage*; D012867:Skin / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D039521:CD11c Antigen; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D019444:Vaccines, DNA; D012710:Serum Albumin, Bovine; D010047:Ovalbumin