THE MENINGOCOCCAL TRANSFERRIN-BINDING PROTEIN-1 AND PROTEIN-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 meni ngitidis 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 previo usly 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 meningococc al vaccines. Protection against meningococcal infection has been corre lated with serum bactericidal antibodies, therefore, it is important f or these vaccine candidates to generate such antibodies. We have previ ously raised rabbit and murine polyclonal monospecific antisera agains t the Tbps of strain SD (B:15:P1.16) which showed varying degrees of c ross-reactivity on immunoblots between the Tbp1 and/or Tbp2 molecules of different heterologous strains from various serogroups, types and s ubtypes. The ability of these antisera to kill meningococci were teste d by incubating live organisms (grown to log phase under iron-restrict ion) with the antisera in the presence of a human complement source (s erum from an agammaglobulinaemic patient). The antisera killed the hom ologous and the majority of the examined heterologous strains with var ying efficiency, with MO obvious correlation with the identity of the strains or the Tbp isotypes which vary between strains. Although the a nimal anti-Tbp antibodies failed to kill some meningococcal strains, i t is not clear how human anti-Tbp antibodies would behave. The mouse a ntiserum was able to kill some heterologous stains against which it on ly had detectable anti-Tbp1 and not anti-Tbp2 antibodies, as seen on W estern blots. Furthermore, the rabbit antiserum was able to kill both Tbp1 and Tbp2 mutants of strain B16B6 (B:2a:P1.2) to almost the same l evel as the wild type strain, indicating that both components of the t ransferrin receptor (Tbp1 and Tbp2) are most likely, to be surface acc essible and capable of generating bactericidal antibodies which can ki ll homologous and heterologous strains. These results strongly support consideration of these Tbps as furtive vaccine components.