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  A modular synthetic route to size-defined immunogenic Haemophilus influenzae b antigens is key to the identification of an octasaccharide lead vaccine candidate

Baek, J. Y., Geissner, A., Rathwell, D. C. K., Meierhofer, D., Pereira, C. L., & Seeberger, P. (2018). A modular synthetic route to size-defined immunogenic Haemophilus influenzae b antigens is key to the identification of an octasaccharide lead vaccine candidate. Chemical Science, 9(5), 1279-1288. doi:10.1039/C7SC04521B.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-9188-1 Version Permalink: http://hdl.handle.net/21.11116/0000-0001-4337-6
Genre: Journal Article

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© Royal Society of Chemistry 2017

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 Creators:
Baek, Ju Yuel 1, Author
Geissner, Andreas 1, 2, Author
Rathwell, Dominea C. K. 1, 2, Author
Meierhofer, David3, Author              
Pereira, Claney L. 1, 4, Author
Seeberger , Peter 1, 2, Author
Affiliations:
1Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany , ou_persistent22              
2Freie Universität Berlin, Department of Chemistry and Biochemistry, 14195 Berlin, Germany, ou_persistent22              
3Mass Spectrometry (Head: David Meierhofer), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479669              
4Vaxxilon Deutschland GmbH, 12489 Berlin, Germany, ou_persistent22              

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 Abstract: The first glycoconjugate vaccine using isolated glycans was licensed to protect children from Haemophilus influenzae serotype b (Hib) infections. Subsequently, the first semisynthetic glycoconjugate vaccine using a mixture of antigens derived by polymerization targeted the same pathogen. Still, a detailed understanding concerning the correlation between oligosaccharide chain length and the immune response towards the polyribosyl-ribitol-phosphate (PRP) capsular polysaccharide that surrounds Hib remains elusive. The design of semisynthetic and synthetic Hib vaccines critically depends on the identification of the minimally protective epitope. Here, we demonstrate that an octasaccharide antigen containing four repeating disaccharide units resembles PRP polysaccharide in terms of immunogenicity and recognition by anti-Hib antibodies. Key to this discovery was the development of a modular synthesis that enabled access to oligosaccharides up to decamers. Glycan arrays containing the synthetic oligosaccharides were used to analyze anti-PRP sera for antibodies. Conjugates of the synthetic antigens and the carrier protein CRM197, which is used in licensed vaccines, were employed in immunization studies in rabbits.

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Language(s): eng - English
 Dates: 2017-12-052017-12-112018-02-07
 Publication Status: Published in print
 Pages: 10
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1039/C7SC04521B
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Title: Chemical Science
  Other : Chem. Sci.
Source Genre: Journal
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Publ. Info: Cambridge, UK : Royal Society of Chemistry
Pages: - Volume / Issue: 9 (5) Sequence Number: - Start / End Page: 1279 - 1288 Identifier: ISSN: 2041-6520
CoNE: https://pure.mpg.de/cone/journals/resource/2041-6520