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Issue 5, 2018
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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

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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.

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

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Publication details

The article was received on 18 Oct 2017, accepted on 05 Dec 2017 and first published on 11 Dec 2017


Article type: Edge Article
DOI: 10.1039/C7SC04521B
Citation: Chem. Sci., 2018,9, 1279-1288
  • Open access: Creative Commons BY license
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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

    J. Y. Baek, A. Geissner, D. C. K. Rathwell, D. Meierhofer, C. L. Pereira and P. H. Seeberger, Chem. Sci., 2018, 9, 1279
    DOI: 10.1039/C7SC04521B

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