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A Semi-Synthetic Glycoconjugate Vaccine Candidate for Carbapenem-Resistant Klebsiella pneumoniae.


ABSTRACT: 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.

SUBMITTER: Seeberger PH 

PROVIDER: S-EPMC5819008 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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A Semi-Synthetic Glycoconjugate Vaccine Candidate for Carbapenem-Resistant Klebsiella pneumoniae.

Seeberger Peter H PH   Pereira Claney L CL   Khan Naeem N   Xiao Guozhi G   Diago-Navarro Elizabeth E   Reppe Katrin K   Opitz Bastian B   Fries Bettina C BC   Witzenrath Martin M  

Angewandte Chemie (International ed. in English) 20171005 45


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 hexasacchar  ...[more]

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