In vivo human immune response to transferrin-binding protein 2 and other iron-regulated proteins of Neisseria meningitidis

Abstract

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.

Immunization with the Recombinant PorB Outer Membrane Protein Induces a Bactericidal Immune Response against Neisseria meningitidis

“…The outer membrane proteins that have been reported to be recognized by the human immune response during infection are the PorA, PorB, Opc, and iron-regulated proteins (13,32). In human trials, current experimental vaccines based on PorA induce immunity that is subtype restricted (32) and may also be influenced by further intrasubtype variations (26).…”

The Gonococcal Fur-Regulated tbpA and tbpB Genes Are Expressed during Natural Mucosal Gonococcal Infection

“…that TbpB should be considered as a candidate for a possible vaccine against N. meningitidis infection (1)(2)(3)19). TbpB antibodies can be measured in convalescent-phase sera from patients with meningococcal disease (18,19,22); they are protective in a mouse model of infection, and they are also bactericidal in laboratory animals (24). However, TbpB is highly variable in different strains of N. gonorrhoeae and, taken together with lower tbpB transcript amounts produced in subject samples, may explain why we observed lower titers of IgG antibody against TbpB antigen than against TbpA.…”

Allelic Diversity of the Two Transferrin Binding Protein B Gene Isotypes among a Collection of Neisseria meningitidis Strains Representative of Serogroup B Disease: Implication for the Composition of a Recombinant TbpB-Based Vaccine

“…It has been shown that antibodies to meningococcal Tbp complexes and to isolated proteins have been detected in both patients and carriers and that these antibodies were able to cross-react with TbpA or TbpB isolated from different meningococci (3,11,16,19). However, in all cases, these conclusions were based on Western blot analysis or enzyme-linked immunosorbent assay (ELISA) performed on purified Tbp complexes.…”