Intranasal immunization against Haemophilus influenzae and Moraxella catarrhalis

摘要

Nontypeable Haemophilus influenzae and Moraxella catarrhalis colonize and infect human mucosal membranes. To improve protection against these pathogens, we have explored the capacity of vaccines to elicit an immune response when intranasally delivered. In these studies, we immunized Balb/c mice with mixtures of the H. influenzae (NTHi) P4 and P6 OMPs and the M. catarrhalis UspA2 serum resistance factor. The addition of an adjuvant was needed to achieve an acceptable response. While detoxified cholera toxin adjuvants (CT-CRM's) induced the strongest immune response, other adjuvants such as the MPL homologues also elicited good responses. When mixed with these adjuvants, the antigen mixture elicited high antibody levels in the serum and mucosal fluids of mice, as well as serum complement-dependent bactericidal activity. The intranasally immunized mice also exhibited a capacity to limit colonization by the two bacterial species upon challenge. These results suggest that an efficacious intranasally delivered vaccine can be developed for people. However, to determine if similar responses can be elicited in people, the intranasal delivery of these antigens and adjuvants needs to be subjected to a clinical trial.