A single nasal dose of fms-like tyrosine kinase receptor-3 ligand, but not peritoneal application, enhances nontypeable Haemophilus influenzae-specific long-term mucosal immune responses in the nasopharynx

Abstract

Nasal vaccination is an effective therapeutic regimen for preventing otitis media. In the development of nasal vaccine, an appropriate adjuvant is required. In the present study, we examined the efficacy of fms-like tyrosine kinase receptor-3 ligand (Flt3L) as a mucosal adjuvant. Flt3L was administered intranasally or peritoneally to mice, which were then immunized intranasally with P6 protein of nontypeable Haemophilus influenzae (NTHi), and P6-specific immune responses were examined. In addition, NTHi challenges were performed and the level of NTHi was quantified in nasal washes. Nasal application of Flt3L induced an increase in the number of dendritic cells in nasal-associated lymphoid tissue. P6-specific nasal wash immunoglobulin (Ig)A and serum IgG titers were elevated significantly after nasal immunization. Enhanced NTHi clearance from the nasopharynx was also observed. The effect of nasal vaccination with P6 combined with nasal Flt3L application was prolonged. These results indicate the potential of Flt3L as an effective mucosal adjuvant and suggest that nasal vaccination with P6 in combination with nasal Flt3L might be an effective regimen for the induction of NTHi-specific protective immunity.