The meningococcal transferrin-binding proteins 1 and 2 are both surface exposed and generate bactericidal antibodies capable of killing homologous and heterologous strains.
When grown in vivo, or under iron-restriction in vitro, Neisseria meningitidis expresses a number of iron-regulated outer membrane proteins, including two transferrin-binding proteins (Tbp1 and Tbp2). The Tbps are highly specific receptors for human transferrin and we have previously demonstrated their immunogenicity in humans and animals and their exposure on the surface of the organism. There is a growing interest in incorporating these Tbps in future outer membrane-based meningococcal vaccines. Protection against meningococcal infection has been correlated with serum bactericidal antibodies, therefore, it is important for these vaccine candidates to generate such antibodies. We have previously raised rabbit and murine polyclonal monospecific antisera against the Tbps of strain SD (B:15:P1.16) which showed varying degrees of cross-reactivity on immunoblots between the Tbp1 and/or Tbp2 molecules of different heterologous strains from various serogroups, types and subtypes. The ability of these antisera to kill meningococci were tested by incubating live organisms (grown to log phase under iron-restriction) with the antisera in the presence of a human complement source (serum from an agammaglobulinaemic patient). The antisera killed the homologous and the majority of the examined heterologous strains with varying efficiency, with no obvious correlation with the identity of the strains or the Tbp isotypes which vary between strains. Although the animal anti-Tbp antibodies failed to kill some meningococcal strains, it is not clear how human anti-Tbp antibodies would behave. The mouse antiserum was able to kill some heterologous stains against which it only had detectable anti-Tbp1 and not anti-Tbp2 antibodies, as seen on Western blots. Furthermore, the rabbit antiserum was able to kill both Tbp1 and Tbp2 mutants of strain B16B6 (B2a:P1.2) to almost the same level as the wild type strain, indicating that both components of the transferrin receptor (Tbp1 and Tbp2) are most likely to be surface accessible and capable of generating bactericidal antibodies which can kill homologous and heterologous strains. These results strongly support consideration of these Tbps as future vaccine components.
Ala'Aldeen
D A
DA
Division of Microbiology, Queen's Medical Centre, Nottingham, UK.
Borriello
S P
SP
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis* / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000276:immunology*; D001770:Blood Bactericidal Activity / Q000235:genetics; D002352:Carrier Proteins / Q000737:chemistry / Q000276:immunology*; D003429:Cross Reactions / Q000235:genetics; D007106:Immune Sera / Q000235:genetics / Q000494:pharmacology; D033862:Iron-Binding Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009345:Neisseria meningitidis / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D011817:Rabbits; D013045:Species Specificity; D033863:Transferrin-Binding Proteins
D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D007106:Immune Sera; D033862:Iron-Binding Proteins; D033863:Transferrin-Binding Proteins