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  Synthetic oligosaccharide-based vaccines protect mice from clostridioides difficile infections

Bröcker, F., Wegner, E., Silva Seco, B. M., Kapłonek, P., Bräutigam, M., Ensser, A., et al. (2019). Synthetic oligosaccharide-based vaccines protect mice from clostridioides difficile infections. ACS Chemical Biology, 14(12), 2720-2728. doi:10.1021/acschembio.9b00642.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-16B4-7 Version Permalink: http://hdl.handle.net/21.11116/0000-0006-56BD-5
Genre: Journal Article

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 Creators:
Bröcker, Felix1, Author              
Wegner, Erik, Author
Silva Seco, Bruna Mara2, Author              
Kapłonek, Paulina2, Author              
Bräutigam, Maria2, Author              
Ensser, Armin, Author
Pfister, Frederick, Author
Daniel, Christoph, Author
Martin, Christopher E.2, Author              
Mattner, Jochen, Author
Seeberger, Peter H.2, Author              
Affiliations:
1Chakkumal Anish, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863299              
2Peter H. Seeberger - Vaccine Development, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863308              

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 Abstract: Infections with Clostridioides difficile (formerly Clostridium difficile) have risen 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 di- to hexasaccharides, were conjugated to CRM197, 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 anti-glycan 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.

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Language(s): eng - English
 Dates: 2019-11-062019
 Publication Status: Published in print
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 Identifiers: DOI: 10.1021/acschembio.9b00642
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Title: ACS Chemical Biology
Source Genre: Journal
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Publ. Info: Washington, D.C. : American Chemical Society
Pages: - Volume / Issue: 14 (12) Sequence Number: - Start / End Page: 2720 - 2728 Identifier: ISSN: 1554-8929