Vaccine potential of proteins encoded on a virulence-associated genomic island in Neisseria meningitidis

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Recent advances in the epidemiology of Neisseria meningitidis, the agent of cerebrospinal meningitis, have shown that meningococcal disease is caused by only a few of the hundreds of clonal lineages defined. However, the molecular basis for the increased pathogenic potential of these hypervirulent strains is as yet unknown. In an attempt to find an answer to this question we have used microarray technology to identify genes and genetic regions associated with strains of increased pathogenic potential. We have compared meningococci belonging to the defined epidemic clonal groups, and isolated from clinical cases of meningococcal disease to strains isolated from carriers and belonging to groups which have not been associated with meningococcal disease. A genomic comparison of 50 strains brought to light a genetic island consisting of six ORFs, which was present in almost all the virulent strains and absent from almost all the carrier isolates. Several of the proteins are predicted to be membrane associated, and at least one is probably surface-exposed. This, together with their association with epidemic meningococcal strains, make these antigens ideal vaccine candidates. We will investigate their role in pathogenesis using standard in vitro models of meningococcal virulence - resistance to the bactericidal effect of complement and interaction with human cell monolayers. The genes will be cloned, and the expressed proteins used to develop antisera for use in assays for their vaccine potential.

Results from this study have been published in a scientific journal as follows:

Bille E, Zahar JR, Perrin A, Morelle S, Kriz P, Jolley KA, Maiden MC, Dervin C, Nassif X, Tinsley CR.
A chromosomally integrated bacteriophage in invasive meningococci.
J Exp Med 2005 Jun 20;201(12):1905-13.
http://www.jem.org/cgi/reprint/201/12/1905.pdf