EVALUATION OF RECOMBINANT TRANSFERRIN-BINDING PROTEIN-B VARIANTS FROMNEISSERIA-MENINGITIDIS FOR THEIR ABILITY TO INDUCE CROSS-REACTIVE ANDBACTERICIDAL ANTIBODIES AGAINST A GENETICALLY DIVERSE COLLECTION OF SEROGROUP-B STRAINS

Transferrin-binding protein B (TbpB) is a surface-exposed protein, var iable among strains of Neisseria meningitidis, that has been considere d as a vaccine candidate, To define a TbpB molecule that would give ri se to broadly cross-reactive antibodies with TbpB of many strains, spe cific antisera were produced against three recombinant TbpB variants f rom strain M982: one corresponding to the full-length TbpB; one in whi ch stretches of amino acids located in the central part of the molecul e, described as hypervariable, have been deleted; and one correspondin g to the N-terminal half of the molecule, described as the human trans ferrin binding domain, The reactivity of these antisera against 58 ser ogroup B strains with a 2.1-kb tbpB gene representing different genoty pes, serotypes, and subtypes and different geographic origins was test ed on intact meningococcal cells, In parallel, the bactericidal activi ty of the antisera was evaluated against 15 of the 58 strains studied, Of the 58 strains, 56 (98%) reacted with the antiserum specific for t he N-terminal half of TbpB M982; this antiserum was bactericidal again st 9 of 15 strains (60%), On the other hand, 43 of 58 strains reacted with the antiserum raised to full-length TbpB while 12 of 15 (80%) wer e killed with this antiserum, The antiserum specific to TbpB deleted o f its central domain gave intermediate results, with 53 of 58 strains (91.3%) recognized and 10 of 15 (66.6%) killed, These results indicate that the N-terminal half of TbpB was sufficient to induce cross-react ive antibodies reacting with the protein on meningococcal cells but th at the presence of the C-terminal half of the protein is necessary for the induction of cross-bactericidal antibodies.