Syntheses of Salmonella Paratyphi A Associated Oligosaccharide Antigens and Development towards Anti-Paratyphoid Fever Vaccines

Chemistry. 2020 Dec 4;26(68):15953-15968. doi: 10.1002/chem.202002401. Epub 2020 Oct 22.


With the emergence of multidrug resistant Salmonella strains, the development of anti-Salmonella vaccines is an important task. Currently there are no approved vaccines against Salmonella Paratyphi A, the leading cause of paratyphoid fever. To fill this gap, oligosaccharides corresponding to the O-polysaccharide repeating units from the surface of Salmonella Paratyphi A have been synthesized through convergent stereoselective glycosylations. The synthetic glycan antigen was conjugated with a powerful immunogenic carrier system, the bacteriophage Qβ. The resulting construct was able to elicit strong and long-lasting anti-glycan IgG antibody responses, which were highly selective toward Salmonella Paratyphi 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 the O-acetyl modifications on the backbone are important for recognition by antibodies elicited by a Qβ-tetrasaccharide conjugate. Immune sera provided excellent protection to mice from lethal challenge with Salmonella Paratyphi A, highlighting the potential of the synthetic glycan-based vaccine.

Keywords: bacteria; biochemistry; glycosylation; salmonella paratyphi A; synthesis; vaccine.

MeSH terms

  • Animals
  • Antibodies, Bacterial / immunology
  • Antigens, Bacterial / immunology
  • Mice
  • Oligosaccharides* / immunology
  • Paratyphoid Fever* / prevention & control
  • Salmonella paratyphi A* / immunology
  • Typhoid-Paratyphoid Vaccines* / administration & dosage
  • Typhoid-Paratyphoid Vaccines* / chemistry
  • Vaccines, Synthetic


  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Oligosaccharides
  • Typhoid-Paratyphoid Vaccines
  • Vaccines, Synthetic