Details

Autor(en) / Beteiligte

• Dhara, Debashis
• Baliban, Scott M.
• Huo, Chang‐Xin
• Rashidijahanabad, Zahra
• Sears, Khandra T.
• Nick, Setare Tahmasebi
• Misra, Anup Kumar
• Tennant, Sharon M.
• Huang, Xuefei

Titel

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

Ist Teil von

• Chemistry : a European journal, 2020-12, Vol.26 (68), p.15953-15968

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Wiley Online Library

Beschreibungen/Notizen

• 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. Salmonella Paratyphi A associated cell‐surface glycans have been synthesized for the first time through convergent stereoselective glycosylation reactions. The synthetic glycan was conjugated with a powerful immunogenic carrier, that is, bacteriophage Qβ. The resulting conjugate induced high levels of IgG antibodies in mice and rabbits against the glycan. Sera from immunized rabbits effectively protected mice from bacterium induced death.