High-Throughput Identification and Characterization of Novel Vaccine Candidates Against Bacterial Pathogens
Genomics has revolutionized the way novel candidates are identified for the development of efficacious vaccines. Reverse vaccinology, whereby all candidates of interest are identified by analysis of a pathogen's genome, enables characterization of many candidates simultaneously. It accelerates the initial steps of vaccine development and greatly increases the chances of obtaining reliable candidates or cocktails thereof as an end result. The gene complement the pathogen is analyzed to predict surface-exposed proteins. These are expressed in vitro and used to immunize mice. Antisera are tested in functional assays to verify their potential as vaccine candidates. The availability of one or two genome sequences for any given pathogen provides access to strain-specific vaccine candidates but often fails to identify candidates that would confer general protection. Analysis of the genome of multiple strains of a given pathogen is more informative and leads to the concept of the pan-genome. Comparative analysis of eight strains of group B Streptococcus (GBS) reveals a core genome of 1800 genes present in all strains, while 20% of the genes are dispensable (absent in one or more strains). Each genome displays an average of 33 unique genes indicating that the species' gene repertoire, or "pan-genome", is extremely large. The same result was obtained with group A Streptococcus and other species. Overall, the availability of eight complete genomes of a single species unveiled 26% more information than any single isolate. Thus, the genome sequence of multiple, independent isolates is required to understand the global complexity of a bacterial species and gain access to relevant virulence determinants and protective antigens.
