A Synthetic Carbohydrate-Protein Conjugate Vaccine Candidate against Klebsiella pneumoniae Serotype K2

Mettu Ravinder, Kuo Shiang Liao, Yang Yu Cheng, Sujeet Pawar, Tzu Lung Lin, Jin Town Wang, Chung Yi Wu*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

15 Scopus citations

Abstract

Klebsiella pneumoniae causes pneumonia and liver abscesses in humans worldwide and contains virulence factor capsular polysaccharides and lipopolysaccharides linked to the cell wall. Although capsular polysaccharides are good antigens for vaccine production and capsular oligosaccharides conjugate vaccines are proven effective against infections caused by encapsulated pathogens, there is still no Klebsiella pneumoniae vaccine available. One obstacle is that the capsular polysaccharide of a dominated Klebsiella pneumoniae serotype K2 is difficult to synthesize chemically due to the three 1,2-cis linkages in its structure. In this study, we successfully synthesized K2 capsular polysaccharides from tetra- to octasaccharides in highly a stereoselective manner. Subsequently, three synthesized glycans were conjugated to DT protein to provide glycoconjugate vaccine candidates (DT-Hexa, DT-Hepta, and DT-Octa) that were used in in vivo immunization experiments in mice. The results of immunized studies showed all three glycoconjugates elicited antibodies that recognized all of the synthetic glycans at 1:200-fold dilution. Particularly, the DT-Hepta conjugate elicited a higher level of antibodies that can recognize longer glycan (octasaccharide) even at 1:12800-fold dilution and exhibited good bactericidal activity. Our results concluded that heptasaccharide is the minimal epitope and a potential candidate for the vaccine against the K2 sero group of Klebsiella pneumoniae.

Original languageEnglish
Pages (from-to)15964-15997
Number of pages34
JournalJournal of Organic Chemistry
Volume85
Issue number24
DOIs
StatePublished - 18 12 2020
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2020 American Chemical Society.

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