The first, and by far the most serious problem, is that the development of a conjugate vaccine against the serogroup B polysaccharide is precluded by a combination of the poor immunogenicity of this polysaccharide and safety concerns, as it is identical to a host antigen NCAM, which decorates foetal neural tissues [49]. Further, a number of quite different clonal complexes that express serogroup B have been associated with disease and over the last decades several have emerged and spread globally in succession [16]. To date, all of the ‘serogroup B substitute’ p38 MAPK inhibitor vaccines that have been implemented have been based on the proteins expressed on the surface of a particular meningococcal strain [50], [51] and [52].

These provide protection against disease caused by that strain and close relatives, i.e. members of the same clonal complex that express similar antigenic variants, but not against others [53]. More sophisticated formulations that increase

the coverage against serogroup B meningococci are being aggressively developed [54] and [55]. It will be interesting PD0332991 to learn whether these vaccines will be able to interrupt transmission to the extent that eradication or elimination would be possible. The eradication of all carried meningococci is almost certainly neither achievable nor desirable: the control, elimination, or eradication of particular invasive meningococci is a more realistic goal, given that a limited number of clonal complexes and serogroups cause most meningococcal disease. However, even this goal is likely to be difficult and requires more research and great political will to achieve. In terms of practicability and desirability, the MenaAfriVac vaccine and its introduction indicates how epidemic serogroup A disease can potentially

be eliminated or and eradicated. The other serogroups are more problematic. Serogroup C is the next most likely candidate, although the biology and logistics are less favourable than for serogroup A. Serogroups Y and W could be targeted, but the cost benefit of this is less clear at the current time. In principle a serogroup X vaccine could be developed, but whether the disease burden is sufficient to warrant its introduction at a scale sufficient for eradication of group X meningococci is doubtful. Finally, and perhaps most problematically, no tools currently exist for controlling serogroup B meningococci per se, and although it may be possible to develop vaccines that target particular or even most serogroup B-associated clonal complexes, thereby substantially reducing disease burden, eradicating all group B meningococci from carriage globally is unlikely to be feasible. Consequently, a world free of invasive meningococci remains an alluring but still distant prospect, although a world with appreciably less meningococcal disease is an achievable and worthwhile goal in the immediate future.