IMMUNIZATION WITH OUTER-MEMBRANE PROTEIN P6 FROM NONTYPABLE HAEMOPHILUS-INFLUENZAE INDUCES BACTERICIDAL ANTIBODY AND AFFORDS PROTECTION IN THE CHINCHILLA MODEL OF OTITIS-MEDIA

The role of nontypeable Haemophilus influenzae (NTHi) outer membrane p rotein (OMP) P6 in the pathogenesis of otitis media (OM) has not been defined, OMPs, fimbriae, pill, and lipooligosaccharide are several typ es of surface antigens of NTHi that are currently being evaluated as p otential vaccine candidates, P6 is antigenically conserved among both nontypeable and type b H. influenzae strains and elicits bactericidal as well as protective antibodies; however, initial evaluation of a vac cine mixture of P6 combined with other NTHi OMPs failed to induce bact ericidal antibody or protection in the chinchilla model of OM. We unde rtook an assessment of the ability of immunization with isolated P6 li poprotein alone to confer protection, Chinchillas were immunized with P6 and challenged 10 days after the final immunization with either 3 x 10(3) CFU of NTHi delivered directly into the middle ear to induce OM or 5 x 10(8) CFU of NTHi delivered intranasally to establish nasophar yngeal colonization, AII immunized animals responded with elevated ser um titers of anti-P6 antibody, which also demonstrated bactericidal ac tivity against homologous as well as a heterologous NTHi isolate, By 1 4 days post-transbullar challenge, the number of chinchillas with midd le ear fluid and the incidence of NTHi culture-positive middle ear flu ids,were reduced 48 and 51%, respectively, in the P6-immunized chinchi llas relative to the sham immunized cohort. Nasopharyngeal colonizatio n levels were comparable in the two cohorts, These data demonstrate th at active immunization with P6 results in the production of NTHi-speci fic bactericidal antibody in the chinchilla and also affords a reducti on in the incidence of NTHi-induced OM; however, parenteral immunizati on does not appear to affect the extent or duration of nasopharyngeal colonization by NTHi.