Synthesis of MenA carba-analogues and native MenX oligomers for improved anti-meningococcal vaccines

The major task of the ESR selected with this call will be the synthesis of Neisseria meningitidis A (MenA) carba-analogues and Neisseria meningitidis X (MenX) oligomers longer than three repeating units and with an approach suitable for automation. MenA is a major cause of meningitis in children. The phosphodiester linkages bridging the different repeating units render the native MenA polymer chemically labile in water. Consequently, most of the glycoconjugate vaccines comprising this polysaccharide have been licensed as lyophilized formulations. Stabilization of glycosyl 1-O-phosphates, which would make feasible a liquid formulation, can be achieved using carba-sugar analogues, where a methylene group replaces the pyranose oxygen atom. A major objective will also be the study of the acetylation for the MenA structures, which is considered a relevant feature to achieve production of functional antibodies.
MenX is recently emerged as a substantial threat for public health and epidemic potential. It has been demonstrated that a potent candidate for the development of a glycoconjugate vaccine against MenX disease can be provided by coupling long chain oligosaccharides from MenX polysaccharide to a protein carrier, and the trimer is the minimal fragment which can evoke production of bactericidal antibodies.
The interaction of the prepared oligomers with specific mAbs will be studied to identify minimal requirement for efficacy.
Planned secondments for this job are in Leiden (University of Leiden, NL), in Lisbon (Institute of Molecular Medicine, PT), and in Siena (GSK Vaccines, IT).

The fellow must not have resided in the country where the research training activities will take place for more than 12 months in the 3 years immediately prior to the recruitment date (and not have carried out their main activity (work, studies, etc.) in that country).
Experience eligibility requirement: Eligible applicants must have less than 4 years research experience (Early Stage Researcher) at the signature of the contract (measured from the time the Master’s degree has been obtained).
Eligible applicants must not have a PhD yet.