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.