Resistance to influenza A virus infection by antigen-conjugated CpG oligonucleotides, a novel antigen-specific immunomodulator.
Oligodeoxynucleotides (ODN) containing CpG motifs (CpG) act as modulators that bias the immune response towards a Th1-dominant phenotype. To investigate this effect further, we examined the protective effects of a covalently linked conjugate between CpG-ODN and HA-2kd antigen in mice infected with influenza A virus. The conjugated form of CpG-ODN and HA-2kd was more efficient in regulating influenza A virus than the unconjugated mixture of CpG-ODN and HA-2kd. The antigen-conjugated CpG-ODN induced an immune response with a Th1-dominant cytokine pattern characterized by the secretion of high levels of HA-2kd-specific interferon-gamma and IgG2a (Th1), which were only slightly induced by HA-2kd alone. These findings support the use of CpG-ODN-Ag conjugates as novel Ag-specific immunomodulators and suggest that CpG-ODN-HA-2kd might be a promising immune therapy for patients with influenza virus.
Hayashi
Mieko
M
Department of Life and Environmental Sciences, Faculty of Engineering, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan.
Satou
Emi
E
Ueki
Ryouji
R
Yano
Mayuka
M
Miyano-Kurosaki
Naoko
N
Fujii
Masayuki
M
Takaku
Hiroshi
H
D000818:Animals; D000941:Antigens / Q000737:chemistry; D000998:Antiviral Agents / Q000494:pharmacology*; D016827:CD8 Antigens / Q000096:biosynthesis; D002460:Cell Line; D018899:CpG Islands; D016207:Cytokines / Q000378:metabolism; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000737:chemistry; D007167:Immunotherapy / Q000379:methods*; D007249:Inflammation; D009980:Influenza A virus / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000494:pharmacology*; D009841:Oligonucleotides / Q000494:pharmacology; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D010455:Peptides / Q000737:chemistry; D010641:Phenotype; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D018417:Th1 Cells / Q000276:immunology / Q000821:virology; D013997:Time Factors
D000941:Antigens; D000998:Antiviral Agents; D016827:CD8 Antigens; C408982:CPG-oligonucleotide; D016207:Cytokines; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides; D010455:Peptides; D007371:Interferon-gamma