Assessment of structural requirements in complement-mediated bactericidal events: Towards a global approach to the selection of new vaccine candidates (BacAbs)

High throughput cloning and expression of large sets of genomic ORFs has become a preferred industrial strategy for genome-wide searches of new vaccine candidates. For invasive infections in particular, the aim is to find proteins eliciting antibodies capable of binding to the bacterial cell surface and, through interaction with the complement system, effectively kill the bacteria. However, current data accumulating from reverse vaccinology studies show that only a small fraction of surface-exposed proteins appears to elicit antibodies with bactericidal activity. By using information generated by reverse vaccinology projects within the Consortium the BacAbs project will apply a novel multidisciplinary approach to single out the structural requirements for viable bactericidal vaccine candidates, and will develop bioinformatics tools to predict compliance with such structural requirements. To this end, a systematic analysis of sequence, structure, dynamics and interactions of selected protein targets will be undertaken using as model system serogroup-B Neisseria meningitidis, a pathogen causing septicemia and meningitis, for which no effective vaccine exists. The Consortium comprises an industrial partner with extensive experience on vaccine development, three SMEs with strong expertises on several of the key technological aspects of the project, and five academic partners with internationally recognised tracks on experimental and theoretical studies of protein structure and interactions. By focusing on meningococcal vaccine development, the project can deliver information (knowledge) relevant to Life Sciences and Human Health and provide new tools and improved methods (technology) of potential application to research on other pathogens at the genomic level.