Prospects offered by genome studies for combating meningococcal disease by vaccination.

Abstract

Meningococcal disease was first recognised and Neisseria meningitidis isolated as the causative agent over 100 years ago, but despite more than a century of research, attempts to eliminate this distressing illness have so far been thwarted. The main problem lies in the fact that N. meningitidis usually exists as a harmless commensal inhabitant of the human nasopharynx, the pathogenic state being the exception rather than the norm. As man is its only host, the meningococcus is uniquely adapted to this ecological niche and has evolved an array of mechanisms for evading clearance by the human immune response. Progress has been made in combating the disease by developing vaccines that target specific pathogenic serogroups of meningococci. However, a fully comprehensive vaccine that protects against all pathogenic strains is still just beyond reach. The publication of the genome sequences of two meningococcal strains, one each from serogroups A and B and the imminent completion of a third illustrates the extent of the problems to be overcome, namely the vast array of genetic mechanisms for the generation of meningococcal diversity. Fortunately, genome studies also provide new hope for solutions to these problems in the potential for a greater understanding of meningococcal pathogenesis and possibilities for the identification of new vaccine candidates. This review describes some of the approaches that are currently being used to exploit the information from meningococcal genome sequences and seeks to identify future prospects for combating meningococcal disease.