THE IMPACT OF SALMONELLA POLYSACCHARIDE ANTIGENS STRUCTURE AND CONJUGATION CHEMISTRY ON NTS GLYCOCONJUGATE VACCINES

The Novartis Vaccines Institute for Global Health (NVGH) is working on the development of a bivalent glycoconjugate vaccine against nontyphoidal Salmonellae (NTS) covering the main serovars S. Typhimurium and S. Enteritidis causing invasive disease in Africa. The vaccine is based on the conjugation of the lipopolysaccharide O antigen, the main surface polysaccharide of NTS, with CRM197 as carrier protein. In this contest, my PhD project has been focused in three related aspects: 1) Structural and biological characterization of NTS O antigen purified from different S. Typhimurium and S. Enteritidis strains. 2) Synthesis, characterization and immunological evaluation of a panel of NTS glycoconjugate vaccine variants (OAg source, conjugation chemistry, OAg/protein ratio) to better understand the key factors in glycoconjugate vaccine design required for optimal antibody-mediated immunity. 3) Design of new efficient glycoconjugation methodologies which allow the synthesis of structurally highly-defined glycoconjugate vaccines and simplify the conjugation process.