Role of transferrin receptor from a Neisseria meningitidis tbpB isotype II strain in human transferrin binding and virulence.

Neisseria meningitidis acquires iron through the action of the transferrin (Tf) receptor, which is composed of the Tf-binding proteins A and B (TbpA and TbpB). Meningococci can be classified into isotype I and II strains depending on whether they harbor a type I or II form of TbpB. Both types of TbpB have been shown to differ in their genomic, biochemical, and antigenic properties. Here we present a comparative study of isogenic mutants deficient in either or both Tbps from the isotype I strain B16B6 and isotype II strain M982. We show that TbpA is essential in both strains for iron uptake and growth with iron-loaded human Tf as a sole iron source. No growth has also been observed for the TbpB- mutant of strain B16B6, as shown previously, whereas the growth of the analogous mutant in M982 was similar to that in the wild type. This indicates that TbpB in the latter strain plays a facilitating but not essential role in iron uptake, which has been observed previously in similar studies of other bacteria. These data are discussed in relation to the fact that isotype II strains represent more than 80% of serogroup B meningococcal strains. The contribution of both subunits in the bacterial virulence of strain M982 has been assessed in a murine model of bacteremia. Both the TbpB- TbpA- mutant and the TbpA- mutant are shown to be nonvirulent in mice, whereas the virulence of the TbpB- mutant is similar to that of the wild type.

Clinical evaluation of a group B meningococcal N-propionylated polysaccharide conjugate vaccine in adult, male volunteers.

The safety and immunogenicity of a group B meningococcal vaccine, consisting of N-propionylated (NPr) B capsular polysaccharide conjugated to tetanus toxoid, was tested for the first time, in 17 healthy male volunteers aged between 18 and 40 years. Four escalating dosages of vaccine were tested and each was given as three intramuscular injections at 4-week intervals. The vaccine was well tolerated and induced only mild and transient, dose-dependent, injection-site reactions. One month after the last injection, there was no evidence of the production of autoantibodies or antibodies binding to PSA-NCAM. The vaccine induced an increase in the pre-existing titres of IgM specific to B polysaccharide and NPr B polysaccharide. Moreover, it induced IgG antibodies specific to NPr B polysaccharide, which were undetectable before vaccination. However, no functional activity of vaccine-induced antibodies was demonstrated in bactericidal assays, opsonophagocytic tests or passive protection tests.