Nasal vaccination with CpG oligodeoxynucleotide induces protective immunity against nontypeable Haemophilus influenzae in the nasopharynx

Objectives: Nasal vaccination is an effective therapeutic regimen for preventing otitis media. Since cholera toxin (CT) is toxic, an alternative adjuvant is required for the development of a nasal vaccine. The efficacy of CpG oligodeoxynucleotide (ODN) as a mucosal adjuvant was examined. Methods: Mice were immunized intranasally with P6 protein of nontypeable Haemophilus influenzae (NTHi) and adjuvant, CT, or CpG ODN, and P6-specific antibody responses were examined. The expression of P6-specifie cytokine mRNA in splenic CD4(+) T cells was also determined. In addition, NTHi challenges were performed and the NTHi was quantified in nasal washes. Results: P6-specific IgA in nasal wash and serum IgG titers were elevated significantly after nasal immunization. The IgG1/IgG2a ratio in serum from P6+CpG-immunized mice was less than that of P6+CT-immunized mice. Although IL-6 was expression similarly in both groups, IFN-gamma expression was greater in P6+CpG-immunized mice than in P6+CT-immunized mice. Enhanced clearance of NTHi from the nasopharynx was also shown equally in both groups. Conclusion: These results indicate that CpG ODN might be an effective mucosal adjuvant, acting by mechanisms that are different from CT. These findings suggest that nasal vaccination with P6 and CpG ODN might be an effective regimen for the induction of NTHi-specifie protective immunity.