Syntheses ofSalmonellaParatyphi A Associated Oligosaccharide Antigens and Development towards Anti-Paratyphoid Fever Vaccines

With the emergence of multidrug resistantSalmonellastrains, the development of anti-Salmonellavaccines is an important task. Currently there are no approved vaccines againstSalmonellaParatyphi A, the leading cause of paratyphoid fever. To fill this gap, oligosaccharides corresponding to theO-polysaccharide repeating units from the surface ofSalmonellaParatyphi A have been synthesized through convergent stereoselective glycosylations. The synthetic glycan antigen was conjugated with a powerful immunogenic carrier system, the bacteriophage Q beta. The resulting construct was able to elicit strong and long-lasting anti-glycan IgG antibody responses, which were highly selective towardSalmonellaParatyphi A associated glycans. The availability of well-defined glycan antigen enabled the determination that one repeating unit of the polysaccharide is sufficient to induce protective antibodies, and the paratose residue and/or theO-acetyl modifications on the backbone are important for recognition by antibodies elicited by a Q beta-tetrasaccharide conjugate. Immune sera provided excellent protection to mice from lethal challenge withSalmonellaParatyphi A, highlighting the potential of the synthetic glycan-based vaccine.