THE TRANSFERRIN-BINDING PROTEIN-B OF MORAXELLA-CATARRHALIS ELICITS BACTERICIDAL ANTIBODIES AND IS A POTENTIAL VACCINE ANTIGEN

The transferrin binding protein genes (tbpA and tbpB) from two strains of Moraxella catarrhalis have been cloned and sequenced. The genomic organization of the M. catarrhalis transferrin binding protein genes i s unique among known bacteria in that tbpA precedes tbpB and there is a third gene located between them. The deduced sequences of the M. cat arrhalis TbpA proteins from two strains were 98% identical, while thos e of the TbpB proteins from the same strains were 63% identical and 70 % similar. The third gene, tentatively called orf3, encodes a protein of approximately 58 kDa that is 98% identical between the two strains. The tbpB genes from four additional strains of M. catarrhalis were cl oned and sequenced, and two potential families of TbpB proteins were i dentified based on sequence similarities, Recombinant TbpA (rTbpA), rT bpB, and rORF3 proteins were expressed in Escherichia coli and purifie d, rTbpB was shown to retain its ability to bind human transferrin aft er transfer to a membrane, I,ut neither rTbpA nor rORF3 did. Monospeci fic anti-rTbpA and anti-rTbpB antibodies were generated and used for i mmunoblot analysis, which demonstrated that epitopes of M. catarrhalis TbpA and TbpB were antigenically conserved and that there was constit utive expression of the tbp genes. In the absence of an appropriate an imal model, anti-rTbpA and anti-rTbpB antibodies were tested for their bactericidal activities. The anti-rTbpA antiserum was not bactericida l, but anti-rTbpB antisera were found to kill heterologous strains wit hin the same family. Thus, if bactericidal ability is clinically relev ant, a vaccine comprising multiple rTbpB antigens may protect against M catarrhalis disease.