Identification of new bacterial antigens by a combination of reverse epidemiology and comparative genomics

Xavier Nassif

INSERM U570, Faculté de Médecine Necker-Enfants Malades, Paris.

Vaccines against extra cellular pathogens rely mostly on the induction of an antibody response increasing the bactericidal activity of the serum and/or the opsonophagocytosis by polymorphonuclear For those pathogens the capsular polysaccharide when conjugated to proteins are the most efficient antigens. However for some bacteria, like group B Neisseria meningitidis and K1 Escherichia coli, the polysaccahride capsule is not immunogen and cannot be used for such a purpose. For these infections, the design of a vaccine relies on some other antigens, and the antigen discovery remain the limiting step. Reverse vaccinology takes advantage of the sequence of the genome of bacterial pathogens to make an exhaustive search of the appropriate antigens among the proteins which are likely to be exposed at the bacterial surface. Here we propose a strategy , in which reverse vaccinology is limited to certain regions of the bacterial genome. These regions are selected, using comparative genomic, on the basis that they are not present in commensal bacteria belonging to the same genospecies as the bacteria for which a vaccine is to be engineered.