Synthetic oligosaccharide-based vaccines protect mice from clostridioides difficile infections
| Autor: | Erik Wegner, Bruna M. S. Seco, Felix Broecker, Maria Bräutigam, Christoph Daniel, Frederick Pfister, Paulina Kaplonek, Armin Ensser, Christopher E. Martin, Peter H. Seeberger, Jochen Mattner |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.drug_class Glycoconjugate Synthetic antigen Antibiotics Oligosaccharides 01 natural sciences Biochemistry Microbiology Mice 03 medical and health sciences Immunity In vivo Animals Medicine Colitis chemistry.chemical_classification Vaccines Synthetic biology Clostridioides difficile 010405 organic chemistry business.industry Articles General Medicine Clostridium difficile medicine.disease 0104 chemical sciences Mice Inbred C57BL 030104 developmental biology chemistry Bacterial Vaccines Clostridium Infections biology.protein Molecular Medicine Female Antibody business Glycoconjugates |
| Zdroj: | ACS Chemical Biology |
| Popis: | Open in a separate window Infections with Clostridioides difficile (formerly Clostridium difficile) have increased in incidence, morbidity, and mortality over the past decade. Preventing infections is becoming increasingly important, as frontline antibiotics become less effective and frequently induce recurrence by disrupting intestinal microbiota. The clinically most advanced vaccine approaches prevent symptoms once C. difficile infection is established by inducing immunity to secreted clostridial cytotoxins. However, they do not inhibit bacterial colonization and thereby favor asymptomatic carriage. Synthetic oligosaccharides resembling the C. difficile surface glycans PS-I, PS-II, and PS-III are immunogenic and serve as basis for colonization-preventing vaccines. Here, we demonstrate that glycoconjugate vaccine candidates based on synthetic oligosaccharides protected mice from infections with two different C. difficile strains. Four synthetic antigens, ranging in size from disaccharides to hexasaccharides, were conjugated to CRM197, which is a carrier protein used in commercial vaccines. The vaccine candidates induced glycan-specific antibodies in mice and substantially limited C. difficile colonization and colitis after experimental infection. The glycoconjugates ameliorated intestinal pathology more substantially than a toxin-targeting vaccine. Colonization of the gut by C. difficile was selectively inhibited while intestinal microbiota remained preserved. Passive transfer experiments with anti-PS-I serum revealed that protection is mediated by specific antiglycan antibodies; however, cell-mediated immunity likely also contributed to protection in vivo. Thus, glycoconjugate vaccines against C. difficile are a complementary approach to toxin-targeting strategies and are advancing through preclinical work. |
| Databáze: | OpenAIRE |
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