Semisynthetic Glycoconjugate Vaccine Lead against <i>Klebsiella pneumoniae</i> Serotype O2afg Induces Functional Antibodies and Reduces the Burden of Acute Pneumonia
Carbapenem-resistant <i>Klebsiella pneumoniae</i> (CR-<i>Kp</i>) 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-<i>Kp</i> 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<sub>197</sub>. 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-<i>Kp</i>. 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-<i>Kp</i> expressing O2afg antigen is awaiting preclinical development.
Authors
- Peter H. Seeberger (ORCID: https://orcid.org/0000-0003-3394-8466)
- Bettina C. Fries (ORCID: https://orcid.org/0000-0002-6847-5518)
- Bastian Opitz
- Maria Bräutigam
- Dacheng Shen (ORCID: https://orcid.org/0000-0002-6633-0219)
- Luiz Gustavo Teixeira Alves (ORCID: https://orcid.org/0000-0002-5822-4168)
- Bruna M. S. Seco (ORCID: https://orcid.org/0000-0001-8440-7833)
- Ling Yao (ORCID: https://orcid.org/0000-0002-0482-9604)
- Martin Witzenrath (ORCID: https://orcid.org/0000-0002-9787-5633)
Institutions
- United States Department of Veterans Affairs (US)
- Infectious Disease Research Institute (US)
- Max Planck Institute of Colloids and Interfaces (DE)
- Infectious Disease Consultants (US)
- Northport VA Medical Center (US)
- Office of Infectious Diseases (US)
- German Center for Lung Research (DE)
- Intermolecular (United States) (US)
- Stony Brook University (US)
- Freie Universität Berlin (DE)
- Charité - Universitätsmedizin Berlin (DE)
Publication Details
- Journal
- Journal of the American Chemical Society
- Published
- 2024-12-12
- DOI
- https://doi.org/10.1021/jacs.4c13972
- Citations
- 5
- Primary Topic
- Antibiotic Resistance in Bacteria
- Type
- article
- Field-Weighted Citation Impact
- 0.85
Funders
- Max-Planck-Gesellschaft
- Freie Universität Berlin
- Zhejiang Sci-Tech University
- Deutsches Zentrum für Lungenforschung
- Stony Brook University
- National Institutes of Health