Premium
Syntheses of Salmonella Paratyphi A Associated Oligosaccharide Antigens and Development towards Anti‐Paratyphoid Fever Vaccines
Author(s) -
Dhara Debashis,
Baliban Scott M.,
Huo ChangXin,
Rashidijahanabad Zahra,
Sears Khandra T.,
Nick Setare Tahmasebi,
Misra Anup Kumar,
Tennant Sharon M.,
Huang Xuefei
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202002401
Subject(s) - salmonella , glycan , paratyphoid fever , antigen , microbiology and biotechnology , antibody , virology , biology , conjugate vaccine , typhoid fever , bacteria , immunogenicity , immunology , biochemistry , glycoprotein , genetics
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.