Evaluation of transferrin-binding protein 2 within the transferrin-binding protein complex as a potential antigen for future meningococcal vaccines.
Because the meningococcal transferrin receptor was shown to elicit bactericidal and protective antibodies in laboratory animals, we undertook a study of the protective role of each of the polypeptides within the Tbp1-Tbp2 complex. We developed a procedure to purify from Neisseria meningitidis B16B6 the two proteins in milligram amounts and raised specific antisera in rabbits and mice. Only antisera specific for Tbp2 displayed bactericidal activity against the parent strain. Mice immunized with purified Tbp2 survived a lethal challenge to a similar degree as animals immunized with the Tbp1-Tbp2 complex, demonstrating that Tbp2 played an important role in the protective activity observed with the complex. Both Tbp1- and Tbp2-specific antisera inhibited transferrin binding to the purified receptor in a solid-phase binding assay, suggesting that the antibodies were able to interact with the Tbp1 molecule only when it was removed from its membrane environment. Finally, Tbp2-specific immunoglobulins were able to lower the growth rate of the meningococci when human transferrin was their sole iron source. Therefore, in all four different systems tested, Tbp2 or antibodies specific for Tbp2 displayed biological characteristics close to those of the Tbp1-Tbp2 complex. This suggests that Tbp2 plays an important role in the protective activity of the complex, eliciting antibodies that are not only bactericidal but also inhibitory for meningococcal growth.
Lissolo
L
L
Pasteur Merieux Sérums et Vaccins, Marcy l'Etoile, France.
Maitre-Wilmotte
G
G
Dumas
P
P
Mignon
M
M
Danve
B
B
Quentin-Millet
M J
MJ
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology / Q000302:isolation & purification; D005069:Evaluation Studies as Topic; D033862:Iron-Binding Proteins; D008589:Meningococcal Infections / Q000517:prevention & control*; D051379:Mice; D009345:Neisseria meningitidis / Q000254:growth & development / Q000276:immunology; D011990:Receptors, Transferrin / Q000276:immunology*; D014168:Transferrin / Q000378:metabolism; D033882:Transferrin-Binding Protein B; D033863:Transferrin-Binding Proteins
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D002352:Carrier Proteins; D033862:Iron-Binding Proteins; D011990:Receptors, Transferrin; D014168:Transferrin; D033882:Transferrin-Binding Protein B; D033863:Transferrin-Binding Proteins