Adjuvant effect of multi-CpG motifs on an HIV-1 DNA vaccine.
Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs trigger an immune response characterized by the activation of B cells, NK cells and monocytes/macrophages. Based on evidence that the immunogenicity of DNA vaccines can be augmented by the addition of CpG motifs, 5-20 additional CpG motifs were cloned into a pUC-derived plasmid. Treating bone-marrow derived dendritic cells (BM-DCs) with CpG-enriched plasmids in vitro boosted their expressions of MHC class II molecules, the CD40 and CD86 activation markers. Co-administering the CpG-enriched plasmids with a DNA vaccine encoding the envelope glycoprotein of HIV to BALB/c mice significantly increased HIV-specific cell mediated and humoral immunity. A significant boost was observed when the CpG plasmid was administered either 2 or 4 days after DNA vaccination. Plasmids containing 20 CpG copies were the most effective immune enhancers both in vitro and in vivo. These results suggest that plasmids containing multiple CpG motifs may improve the immunogenicity of DNA vaccines.
Department of Bacteriology, University School of Medicine, Yokohama City, Yokohama 236-0004, Japan.
Yoshitsugu
Y
Kojima
Ke-Qin
KQ
Xin
Takaaki
T
Ooki
Kenji
K
Hamajima
Tomohiro
T
Oikawa
Kaori
K
Shinoda
Tomomi
T
Ozaki
Yuka
Y
Hoshino
Nao
N
Jounai
Masatoshi
M
Nakazawa
Dennis
D
Klinman
Kenji
K
Okuda
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000378:metabolism; D051940:B7-2 Antigen; D001483:Base Sequence; D019013:CD40 Antigens / Q000378:metabolism; D018899:CpG Islands / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006968:Hypersensitivity, Delayed; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D051940:B7-2 Antigen; D019013:CD40 Antigens; C408982:CPG-oligonucleotide; C497965:Cd86 protein, mouse; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D019444:Vaccines, DNA; D007371:Interferon-gamma