The training in WP1 Carbohydrate production builds on the strong UL background in carbohydrate chemistry directed to liquid and solid phase carbohydrate synthesis and analytics of small glycans, as witnessed by the large publication record in carbohydrate synthesis of various bacterial glycan structures from Staphylococcus aureus, Group A Streptococcus, P. aeruginosa, where GSK will provide its historical expertise in polysaccharide purification/isolation/characterization. It will train the ESRs in the chemical modification of proteins, which has been applied to develop a series of commercially available vaccines against H. influenzae type b, S. pneumoniae, N. meningitidis, and candidates at preclinical or clinical level (e.g. Group B Streptococcus, Candida albicans, Clostridium difficile).
Research topics/Work packages
The development of a new vaccine is a very challenging and multidisciplinary process, requiring knowledge of various subjects, including synthetic chemistry, conjugation chemistry, immunology and formulation. The combined expertise of the partners involved in this project, which is not available (to the same level) in the individual organisations, offers state-of-the-art knowledge to the ESRs on all topics, required in the conception of a new anti- bacterial vaccine. The strong coherence of the research programme and work packages ensures that all ESRs will receive training in a multidisciplinary and intersectorial manner.
WP2 Structural glycovaccinology will foster the development of skills in studying carbohydrate-protein interactions with complementary techniques available at the two partners sites, including microarray strategies and NMR/SPR/ITC/ELISA. UL has applied glycoarray techniques to identify epitopes in glycans from Enterococcus faecium and E. faecalis as well as S. aureus, while GSK has used an integrated approach combing X- ray and NMR to elucidate the minimal epitope of Group B Streptococcus type III. The combination of techniques available to the ESRs will train them to analyze and tackle scientific problems from different angles.
WP3 Glycoconjugation: while most of the classic conjugation approaches are based on targeting the abundant lysines and glutamates exposed on the protein surface, typically leading to random conjugation, GSK has recently contributed to the development of new selective conjugation methods, directed at the modification of tyrosine residues or disulfide bridges or of protein with engineered and exposed cysteines. The crystal structure of exotoxin A from PA is available and can be used as starting point for the design of selective conjugation approaches.
The training in WP4 Immunogenicity will be built on GSK’s know-how in vaccine formulation, adjuvant technology, immunochemistry and immunization techniques to provide state-of-the-art education on these complex topics from experts working in these fields. PAVax will combine the above described technologies to gain structural insights in PA/SA polysaccharides and their immunochemical properties but the gathered knowledge and training of the ESRs can be utilized in the conception of new and improved vaccines to various other (antibiotic resistant) target bacteria. The multidisciplinary training will prepare the ESRs not only for future research in vaccinology, but it will provide them with a background suitable to take on any challenging (drug- discovery) project in the Life Sciences. It will train the students in a project “bench-to-bedside” and expose them to the complete drug discovery/development pipeline.