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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. H. (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/21.11116/0000-0000-8403-7 Version Permalink: http://hdl.handle.net/21.11116/0000-0006-6118-2
Genre: Journal Article

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 Creators:
Baek, J. Y.1, Author              
Geissner, A.2, Author              
Rathwell, D. C. K.1, Author              
Meierhofer, D., Author
Pereira, C. L.1, Author              
Seeberger, Peter H.1, Author              
Affiliations:
1Peter H. Seeberger - Vaccine Development, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863308              
2Chakkumal Anish, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863299              

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Free keywords: Open Access
 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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 Dates: 2018-02-07
 Publication Status: Published in print
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 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