Evaluation of recombinant transferrin-binding protein B variants from Neisseria meningitidis for their ability to induce cross-reactive and bactericidal antibodies against a genetically diverse collection of serogroup B strains.
Transferrin-binding protein B (TbpB) is a surface-exposed protein, variable among strains of Neisseria meningitidis, that has been considered as a vaccine candidate. To define a TbpB molecule that would give rise to broadly cross-reactive antibodies with TbpB of many strains, specific antisera were produced against three recombinant TbpB variants from strain M982: one corresponding to the full-length TbpB; one in which stretches of amino acids located in the central part of the molecule, described as hypervariable, have been deleted; and one corresponding to the N-terminal half of the molecule, described as the human transferrin binding domain. The reactivity of these antisera against 58 serogroup B strains with a 2.1-kb tbpB gene representing different genotypes, serotypes, and subtypes and different geographic origins was tested on intact meningococcal cells. In parallel, the bactericidal activity of the antisera was evaluated against 15 of the 58 strains studied. Of the 58 strains, 56 (98%) reacted with the antiserum specific for the N-terminal half of TbpB M982; this antiserum was bactericidal against 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%) were killed with this antiserum. The antiserum specific to TbpB deleted of 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-reactive antibodies reacting with the protein on meningococcal cells but that the presence of the C-terminal half of the protein is necessary for the induction of cross-bactericidal antibodies.
Rokbi
B
B
Pasteur Mérieux Sérums et Vaccins, Marcy-l'Etoile, France.
Mignon
M
M
Maitre-Wilmotte
G
G
Lissolo
L
L
Danve
B
B
Caugant
D A
DA
Quentin-Millet
M J
MJ
D000907:Antibodies, Bacterial / Q000276:immunology*; D000918:Antibody Specificity; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D003429:Cross Reactions; D014644:Genetic Variation; D033862:Iron-Binding Proteins; D009345:Neisseria meningitidis / Q000145:classification / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D012703:Serotyping; D015610:Serum Bactericidal Test; D033882:Transferrin-Binding Protein B; D033863:Transferrin-Binding Proteins
D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D002352:Carrier Proteins; D033862:Iron-Binding Proteins; D011994:Recombinant Proteins; D033882:Transferrin-Binding Protein B; D033863:Transferrin-Binding Proteins