Safety and efficacy of nasal application of CpG oligodeoxynucleotide as a mucosal adjuvant.
OBJECTIVE
Nasal vaccination is an effective regimen to prevent upper respiratory infections. An appropriate adjuvant is required for the development of a nasal vaccine. The safety and efficacy of CpG oligodeoxynucleotide (ODN) as a mucosal adjuvant was examined.


METHODS
Mice were nasally administered various doses of CpG ODN weekly, a total of three times. Histologic changes in the spleen and the nasal mucosa were examined, and the alterations in cell subpopulations were analyzed by flow cytometry. In addition, the mice were nasally immunized with P6 outer membrane protein of nontypeable Haemophilus influenzae (NTHi) and CpG ODN, and P6-specific immune responses were examined.


RESULTS
No inflammation or tissue damage was observed locally or systemically after nasal administration, even with a high dose of CpG ODN. A high dose of CpG ODN induced an increase in CD8+ T cells in the nasal mucosa and B cells in the spleen. When CpG ODN was coadministered with P6, P6-specific mucosal and systemic immune responses were effectively induced, since high levels of the specific IgA and IgG were detected in the nasal wash and serum, respectively.


CONCLUSIONS
These findings suggest that CpG ODN is a safe and effective mucosal adjuvant. Further, nasal vaccination with P6 and CpG ODN might be an effective regimen to prevent upper respiratory infections.
Department of Otolaryngology, Oita University Faculty of Medicine, Idaigaoka, Hazama-machi, Oita, Japan.
Satoru
S
Kodama
Nobuyuki
N
Abe
Takashi
T
Hirano
Masashi
M
Suzuki
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000281:Administration, Intranasal; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D018073:Haemophilus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D012141:Respiratory Tract Infections / Q000276:immunology / Q000517:prevention & control*; D013154:Spleen / Q000276:immunology; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; C408982:CPG-oligonucleotide; D018073:Haemophilus Vaccines; D009838:Oligodeoxyribonucleotides; C069990:P6 outer membrane protein, Haemophilus