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  • Title: A Semi-Synthetic Glycoconjugate Vaccine Candidate for Carbapenem-Resistant Klebsiella pneumoniae.
    Author: Seeberger PH, Pereira CL, Khan N, Xiao G, Diago-Navarro E, Reppe K, Opitz B, Fries BC, Witzenrath M.
    Journal: Angew Chem Int Ed Engl; 2017 Nov 06; 56(45):13973-13978. PubMed ID: 28815890.
    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.
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