A Semi‐Synthetic Glycoconjugate Vaccine Candidate for Carbapenem‐Resistant Klebsiella pneumoniae

Hospital‐acquired infections are an increasingly serious health concern. Infections caused by carpabenem‐resistant Klebsiella pneumoniae (CR‐Kp) are especially problematic, with a 50 % average survival rate. CR‐Kp are isolated from patients with ever greater frequency, 7 % within the EU but 62 % in...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2017-11, Vol.56 (45), p.13973-13978
Main Authors: Seeberger, Peter H., Pereira, Claney L., Khan, Naeem, Xiao, Guozhi, Diago‐Navarro, Elizabeth, Reppe, Katrin, Opitz, Bastian, Fries, Bettina C., Witzenrath, Martin
Format: Article
Language:English
Subjects:
antibiotic resistance
Antibiotics
Antibodies
Bacteria
Enzyme-linked immunosorbent assay
hexasaccharide total synthesis
Immunization
Infections
Klebsiella
Klebsiella pneumoniae
Nosocomial infections
Phagocytosis
Rabbits
Vaccines
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Summary:Hospital‐acquired infections are an increasingly serious health concern. Infections caused by carpabenem‐resistant Klebsiella pneumoniae (CR‐Kp) are especially problematic, with a 50 % average survival rate. CR‐Kp are isolated from patients with ever greater frequency, 7 % within the EU but 62 % in Greece. At a time when antibiotics are becoming less effective, no vaccines to protect from this severe bacterial infection exist. Herein, we describe the convergent [3+3] synthesis of the hexasaccharide repeating unit from its capsular polysaccharide and related sequences. Immunization with the synthetic hexasaccharide 1 glycoconjugate resulted in high titers of cross‐reactive antibodies against CR‐Kp CPS in mice and rabbits. Whole‐cell ELISA was used to establish the surface staining of CR‐Kp strains. The antibodies raised were found to promote phagocytosis. Thus, this semi‐synthetic glycoconjugate is a lead for the development of a vaccine against a rapidly progressing, deadly bacterium. Resisting the Resistant: A hexasaccharide lead antigen has been identified en route to developing a vaccine against carbapenem‐resistant Klebsiella pneumoniae (CR‐Kp), a deadly agent in hospital‐acquired infections.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201700964