In vivo human immune response to transferrin-binding protein 2 and other iron-regulated proteins of Neisseria meningitidis.
When grown under iron restriction, Neisseria meningitidis expresses new outer-membrane proteins, some of which are antigenic and potentially useful as vaccine components. This is particularly relevant to N. meningitidis serogroup B, against which neither polysaccharide nor conjugate vaccines are effective. We investigated recognition of N. meningitidis serogroup B outer-membrane antigens by three sera from patients recovered from meningitis. Recognition of antigens from the homologous strain provided information on in vivo expression during infection and immunogenicity, while cross-reactivity with outer membrane proteins from the other two strains and from another five strains in our collection allowed evaluation of antigenic heterogeneity. Our results demonstrate that transferrin-binding protein 2 (TBP2) is immunogenic in humans, to varying degrees depending on the strain, and that TBP2s (like the equivalent proteins of Haemophilus influenzae type b) are among the most important iron-regulated outer membrane antigens expressed during infection. Other immunogenic outer membrane proteins (some iron-regulated) are also expressed during infection; in a previous study in mouse, three of these proteins (with M(r) of 50, 70 and 77 kDa) did not induce an immune response. Our cross-reactivity data provide some support for Robki et al.'s two-group classification of N. meningitidis strains, and provide evidence against the possibility that the antigenic domains shared by the TBP2s of all N. meningitidis strains induce immune responses in vivo.
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Departamento de Microbiología y Parasitología, Facultad de Farmacia, Universidad de Santiago de Compostela, La Coruña, Spain.
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D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D002555:Cerebrospinal Fluid / Q000382:microbiology; D003429:Cross Reactions; D006801:Humans; D007501:Iron / Q000378:metabolism; D033862:Iron-Binding Proteins; D008585:Meningitis, Meningococcal / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology / Q000382:microbiology; D051379:Mice; D009345:Neisseria meningitidis / Q000145:classification / Q000276:immunology* / Q000302:isolation & purification; D012703:Serotyping; D033882:Transferrin-Binding Protein B; D033863:Transferrin-Binding Proteins
D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D033862:Iron-Binding Proteins; D033882:Transferrin-Binding Protein B; D033863:Transferrin-Binding Proteins; D007501:Iron