Immunization with recombinant transferrin binding protein B enhances clearance of nontypeable Haemophilus influenzae from the rat lung

Nontypeable Haemophilus influenzae (NTHI) is an opportunistic pathogen, and heterogeneity in the surface-exposed immunodominant domains of NTHI protei ns is thought to be associated with the failure of an infection to stimulat e an immune response that is cross protective against heterologous NTHI str ains. The aim of this study was to assess the vaccine potential of a surfac e exposed component of the NTHI human transferrin receptor, TbpB, and to de termine if the antibody response elicited was cross-reactive with heterolog ous strains of NTHI, The efficacy of immunization with a recombinant form o f TbpB (rTbpB) was determined by assessing the pulmonary clearance of viabl e bacteria 4 h after a live challenge with NTHI, There was a significant re duction in the number of viable bacteria in both the bronchoalveolar lavage fluid (34% for the 20-mu g dose and 58% for the 40-mu g dose) and lung hom ogenates (26% for the 20-mu g dose and 60% for the 40-mu g dose) of rats im munized with rTbpB compared to the control animals. While rTbpB-specific an tibodies from immunized rats were nonspecific in the recognition of TbpB fr om six heterologous NTHI strains on Western blots, these antibodies differe d in their ability to block transferrin binding to heterologous strains and to cross-react in bactericidal assays, If bactericidal antibodies are key indicators of the efficacy of the immune response in eliminating NTHI, this data suggests that while immunization with rTbpB stimulates protective res ponses against the homologous isolate, variability in the recognition of Tb pB from heterologous isolates may limit the potential of rTbpB as an NTHI v accine component.