Therapeutic administration of a synthetic CpG oligodeoxynucleotide triggers formation of anti-CpG antibodies.
The synthetic oligodeoxynucleotide CpG 7909, which contains unmethylated cytosine/guanine (CpG) motifs, has potent immunostimulatory effects when coadministered with NY-ESO-1 peptides or recombinant NY-ESO-1 protein, resulting in an enhanced cellular and humoral immune response against the vaccine antigen. In this study, we report the development of anti-CpG-ODN antibodies in 21 of 37 patients who received CpG 7909 either alone or as a vaccine adjuvant. Specific anti-CpG immunoglobulin G (IgG) antibody titers ranged from 1:400 to 1:100,000. The anti-CpG antibodies cross-reacted with other synthetic CpG-ODNs but not with the DNA of mixed bacterial vaccine and were shown to be phosphorothioate backbone specific. Vaccine-related severe side effects observed in some patients were most likely not related to the development of anti-CpG antibodies. In addition, anti-CpG antibodies did not have negative effects on the vaccine immune response. These results show that anti-CpG antibodies develop in humans against short unmethylated CpG dinucleotide sequences after administration of CpG 7909. Our data therefore substantiate the potency of CpG 7909 to directly stimulate human B-cells and suggest that anti-CpG antibody monitoring should be a part of ongoing and planned clinical trials with CpG-ODNs.
II. Medizinische Klinik, Hämatologie-Onkologie, Krankenhaus Nordwest, Frankfurt, Germany.
Julia
J
Karbach
Antje
A
Neumann
Claudia
C
Wahle
Kathrin
K
Brand
Sacha
S
Gnjatic
Elke
E
Jäger
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects; D000906:Antibodies / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000097:blood / Q000276:immunology; D000951:Antigens, Neoplasm / Q000627:therapeutic use; D019496:Cancer Vaccines; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008565:Membrane Proteins / Q000627:therapeutic use; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D022223:Vaccines, Subunit
D000276:Adjuvants, Immunologic; D000906:Antibodies; D000936:Antigen-Antibody Complex; D000951:Antigens, Neoplasm; C408982:CPG-oligonucleotide; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D007074:Immunoglobulin G; D008565:Membrane Proteins; D009838:Oligodeoxyribonucleotides; D022223:Vaccines, Subunit