IMMUNE-RESPONSES IN HUMANS AND ANIMALS TO MENINGOCOCCAL TRANSFERRIN-BINDING PROTEINS - IMPLICATIONS FOR VACCINE DESIGN

The results reported here show that the two meningococcal transferrin- binding proteins (TBP1 and TBP2) generate different immune responses i n different host species and that there is variation in response depen dent on the method of antigen preparation and possibly the route of ad ministration. Mice immunized with either whole cells of Neisseria meni ngitidis SD (B:15:P1.16) or the isolated TBP1-TBP2; complex from the s ame strain produced antisera which, when tested against a representati ve panel of meningococcal isolates by Western blotting (immunoblotting ), recognized some but not all heterologous TBP2 molecules. In contras t, rabbit antisera raised to the same preparations were cross-reactive ,vith almost all the TBP2 molecules. The immune response to TBP1 was a lso host species dependent. Western blot analysis with denatured TBP1 failed to detect antibodies in antisera raised in mice to whole cells or in a rabbit to the TBP1-TBP2 complex but detected broadly cross-rea ctive antibodies in mouse anti-TBP1-TBP2 complex sera and strain-speci fic antibodies in rabbit anti-whole-cell serum. Human convalescent-pha se sera obtained from five patients infected with meningococci of diff erent serogroups and serotypes contained fully cross-reactive antibodi es to TBP2 but no anti-TBP1 antibodies, when examined on Western blots . However, on dot immunoblots, the same patients' sera, as well as the mouse anti-whole cell and the rabbit anti-TBP1-TBP2 complex sera, rea cted with purified biologically active TBP1 of strain SD. This indicat es that native TBP1, a protein which loses its biological and some of its immunological activities when denatured, is immunogenic and that h umans generate cross-reactive antibodies to native epitopes. These obs ervations have important implications for assessing the vaccine potent ial of TBPs and other meningococcal antigens. Conclusions regarding th e usefulness of TBPs as candidate components of meningococcal serogrou p B vaccines based on results from certain animal species such as mice , or on methods such as Western blotting, may have little bearing on t he situation in humans and may lead to some potentially useful antigen s being disregarded.