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Semisynthetic glycoconjugate vaccine lead against klebsiella pneumoniae serotype O2afg induces functional antibodies and reduces the burden of acute pneumonia

Title: Semisynthetic glycoconjugate vaccine lead against klebsiella pneumoniae serotype O2afg induces functional antibodies and reduces the burden of acute pneumonia
Authors: Shen, D.; Silva Seco, B.; Teixeira Alves, L.; Yao, L.; Bräutigam, M.; Opitz, B.; Witzenrath, M.; Fries, B.; Seeberger, P.
Source: Journal of the American Chemical Society
Publication Year: 2024
Collection: Max Planck Society: MPG.PuRe
Description: Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) bacteria are a serious global health concern due to their drug-resistance to nearly all available antibiotics, fast spread, and high mortality rate. O2afg is a major CR-Kp serotype in the sequence type 258 group (KPST258) that is weakly immunogenic in humans. Here, we describe the creation and evaluation of semisynthetic O2afg glycoconjugate vaccine leads containing one and two repeating units of the polysaccharide epitope that covers the surface of the bacteria conjugated to the carrier protein CRM 197 . The semisynthetic glycoconjugate containing two repeating units induced functional IgG antibodies in rabbits with opsonophagocytic killing activity and enhanced complement activation and complement-mediated killing of CR-Kp. Passive immunization reduced the burden of acute pneumonia in mice and may represent an alternative to antimicrobial therapy. The semisynthetic glycoconjugate vaccine lead against CR-Kp expressing O2afg antigen is awaiting preclinical development.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
Availability: https://hdl.handle.net/21.11116/0000-0010-5C65-6; https://hdl.handle.net/21.11116/0000-0010-6AAD-5
Rights: info:eu-repo/semantics/openAccess ; https://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.E25EDAA
Database: BASE