Coping with genetic diversity: the contribution of pathogen and human genomics to modern vaccinology

Lemaire, D.; Barbosa, T.; Rihet, P.

Entire microorganism genome sequences can be obtained relatively inexpensively and quickly, a fact that makes it feasible to have whole genome data available from multiple isolates of a single pathogen. This technological advance has provided the basis for the exciting, newly proposed concept of Pangenome (19) . According to this concept, a bacterial species could be characterized by its global gene repertoire, which contains genes shared by all the strains (core genome) and genes shared by some strains but not all (dispensable genome). Additionally, genetic variants in genes that are found in all strains can be characterized by DNA sequence analysis. This concept has been used to characterize intraspecies diversity in a novel approach for the discovery of new vaccine candidate molecules: Pangenomics reverse vaccinology (20) . Thus, the development of effective, multivalent and broad coverage genome-based vaccines will probably result from approaches that include genomes from multiple isolates from each microbial pathogen. Yet, underrepresented strains not targeted by the multivalent vaccine may become a matter of concern after broad vaccine coverage is established. Serotype replacement, a phenomenon by which minor bacterial serotypes become predominant over time, has been documented after the introduction of the heptavalent anti-pneumococcal conjugate vaccine. It can be attributed to the fact that strains not targeted by the vaccine are able to escape vaccine selective pressure (21) .