There is now considerable evidence to show that in the Neisseria and Haemophilus species, membrane receptors specific for either transferrin or lactoferrin are involved in the acquisition of iron from these glycoproteins. In Neisseria meningitidis, the transferrin receptor appears to consist of two proteins, one of which (TBP 1) has an Mr of 95,000 and the other of which (TBP 2) has an Mr ranging from 68,000 to 85,000, depending on the strain; TBP 2 binds transferrin after sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electroblotting, but TBP 1 does not do so. The relative contributions of these two proteins to the binding reaction observed with intact cells and to iron uptake are presently unknown. However, they are being considered as potential components of a group B meningococcal vaccine. Analogous higherand lowermolecular-weight proteins associated with transferrin binding have been found in N. gonorrhoeae and Haemophilus influenzae. Previous work with polyclonal antibodies raised in mice with whole cells of iron-restricted N. meningitidis showed that the meningococcal TBP 2 exhibits considerable antigenic heterogeneity. Here, we report that antiserum against purified TBP 2 from one strain of N. meningitidis cross-reacts on immunoblotting with the TBP 2 of all meningococcal isolates examined, as well as with the TBP 2 of N. gonorrhoeae. This antiserum also cross-reacted with the TBP 2 of several strains of H. influenzae type b, thus showing the presence of common antigenic domains among these functionally equivalent proteins in different pathogens; no cross-reaction was detected with a purified sample of the human transferrin receptor.

Long term changes in the size of populations of the tsetse Glossina pallidipes Austen and G. longipennis Corti were monitored over a 12 year period at Nguruman in south-western Kenya. Tsetse populations were subject to droughts of varying intensity and, from 1987, to trapping, initially by a research organization, and later by a community-based development project. Populations were mainly sampled using odour-baited biconical traps, with data from other monitoring traps corrected accordingly. Mark-release-recapture studies were carried out to relate trap catches to absolute population size, and to quantify movement between subpopulations. Trypanosomiasis incidence rates in a herd of local cattle were also monitored for much of this period. Trap catches were shown to be well correlated with estimates of absolute population size, with no evidence of any seasonal change in trap efficiency. The intensity of trapping and level of seasonal immigration appeared to be the main determinants of population trends, with effective control being achieved when traps were well maintained. Movement between the two lowland subpopulations was shown to be greater for females, and to be inversely related to temperature. An analytical model was used to investigate the responses of a partially isolated population to trapping pressure. Predictions of a deterministic simulation model demonstrated that the observed changes are consistent with an adult trapping mortality of 4-8% per day, and immigration of 100,000 G. pallidipes females per month in the long rains (April and May), 5000 per month in the short rains (November), and about 500 per month during the dry seasons. Trypanosomiasis incidence in local cattle was greatly reduced during the period of community-based tsetse control. When tsetse were sampled exactly where the cattle were grazing, disease incidence was shown to be linearly related to G. pallidipes catches. Arguments for trap resistance and residual populations were examined, and found to be inconsistent with the data. The future for tsetse control by the Nguruman community is considered.

The results reported here show that the two meningococcal transferrin-binding proteins (TBP1 and TBP2) generate different immune responses in different host species and that there is variation in response dependent on the method of antigen preparation and possibly the route of administration. Mice immunized with either whole cells of Neisseria meningitidis SD (B:15:P1.16) or the isolated TBP1-TBP2 complex from the same strain produced antisera which, when tested against a representative panel of meningococcal isolates by Western blotting (immunoblotting), recognized some but not all heterologous TBP2 molecules. In contrast, rabbit antisera raised to the same preparations were cross-reactive with almost all the TBP2 molecules. The immune response to TBP1 was also 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-reactive antibodies in mouse anti-TBP1-TBP2 complex sera and strain-specific antibodies in rabbit anti-whole-cell serum. Human convalescent-phase sera obtained from five patients infected with meningococci of different serogroups and serotypes contained fully cross-reactive antibodies 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, reacted with purified biologically active TBP1 of strain SD. This indicates that native TBP1, a protein which loses its biological and some of its immunological activities when denatured, is immunogenic and that humans generate cross-reactive antibodies to native epitopes. These observations have important implications for assessing the vaccine potential of TBPs and other meningococcal antigens. Conclusions regarding the usefulness of TBPs as candidate components of meningococcal serogroup B vaccines based on results from certain animal species such as mice, or on methods such as Western blotting, may have little bearing on the situation in humans and may lead to some potentially useful antigens being disregarded.

The ability of Haernophilus influenzae, H. parainfluenzae and H. paraphrophilus to utilize iron complexes, ironproteins and exogenous microbial siderophores was evaluated. In a plate bioassay, all three species used not only ferric nitrate but also the iron chelates ferric citrate, ferric nitrilotriacetate and ferric 2,3-dihydroxybenzoate. Each Haernophilus species examined also used haemin, haemoglobin and haem-albumin as iron sources although only H. influenzae could acquire iron from transferrin or from haemoglobin complexed with haptoglobin. None of the haemophili obtained iron from ferritin or lactoferrin or from the microbial siderophores aerobactin or desferrioxamine B. However, the phenolate siderophore enterobactin supplied iron to both H. parainfluenzae and H. paraphrophilus, and DNA isolated from both organisms hybridized with a DNA probe prepared from the Escherichia coli ferric enterobactin receptor gene fepA. In addition, a monospecific polyclonal antiserum raised against the E. coli 81 kDa ferric enterobactin receptor (FepA) recognized an iron-repressible outer membrane protein (OMP) in H. parainfluenzae of between 80 and 82 kDa (depending on the strain). This anti-FepA serum did not cross-react with any of the OMPs of H. paraphrophilus or H. influenzae. The OMPs of each Haernophilus species were also probed with antisera raised against the 74 kDa Cir or 74 kDa IutA (aerobactin receptor) proteins of E. coli. Apart from one H. parainfluenzae strain (NCTC 10665), in which an OMP of about 80 kDa crossreacted with the anti-IutA sera, no cross-reactivity was observed between Cir, IutA and the OMPs of H. influenzae, H. parairifluenzae or H. paraphrophilus. Thus, H. parainfluenzae and H. paraphrophilus possess a functional enterobactin iron-uptake system, and both siderophore-dependent and siderophore-independent highaffinity iron-sequestering systems are now known to be expressed in the genus Haernophilus.

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