Population studies

Studies o f the population genetics o f N. meningitidis have been biased towards disease-causing strains. However, the majority of meningococci are harmless commensals, hence it is vital that strains isolated from asymptomatic carriers are also examined to enable a complete interpretation of meningococcal population biology. Additionally, given the propensity of Neisseria species to exchange genetic information, it is essential that further isolates of other Neisseria species are

examined. The markers used for such analyses should be chosen to be biologically relevant or to be representative of the total genetic diversity within each strain. The introduction of genetic markers and rapid methods for strain characterisation will be useful both for epidemiological monitoring of outbreaks and for the development of vaccines against meningococcal disease.

6.4 G eneral conclusions

As many investigators from Darwin to Dawkins have found, scientific research often raises as many questions as it answers. This is certainly true o f the work described in this thesis.

At the outset of this study, it was hoped that OMP based vaccines would be the way forward in combatting meningococcal disease, especially against serogroup B and C organisms. The work described in this thesis may suggest that the prognosis for these vaccines is not encouraging, and that other components should be assessed for vaccine potential alongside porin antigens. However, these data have helped to define the processes of porin antigenic variation among meningococci and other species o f Neisseria and have provided valuable information to increase the

understanding of how these organisms evolve in relationship with their human hosts. It requires only a small decrease in the reproductive rate o f the meningococcus to have a major impact on the reduction of disease incidence. Therefore, even if OMP vaccines are only partially effective, they may still have a role in the management of disease. If porin antigenic variation in meningococcal populations can be accurately monitored, it is possible that OMP vaccines could be tailored to protect against prevailing, disease-causing strains.

Although much work remains to be done in the development o f novel vaccines against meningococcal disease, the studies described in this thesis provide an insight into the basic biology o f N. meningitidis that suggests new paths to follow towards this end. Consequently, as our knowledge of meningococcal disease increases, so does our chance of controlling it.

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