A Semi-synthetic Oligosaccharide Conjugate Vaccine Candidate Confers Protection against Streptococcus pneumoniae Serotype 3 Infection

Sharavathi Guddehalli Parameswarappa, Katrin Reppe, Andreas Geissner, Petra Ménová, Subramanian Govindan, Adam D.J. Calow, Annette Wahlbrink, Markus W. Weishaupt, Bopanna Ponnappa Monnanda, Roland Lawrence Bell, Liise Anne Pirofski, Norbert Suttorp, Leif Erik Sander, Martin Witzenrath, Claney Lebev Pereira, Chakkumkal Anish, Peter H. Seeberger

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

The identification of immunogenic glycotopes that render glycoconjugate vaccines protective is key to improving vaccine efficacy. Synthetic oligosaccharides are an attractive alternative to the heterogeneous preparations of purified polysaccharides that most marketed glycoconjugate vaccines are based on. To investigate the potency of semi-synthetic glycoconjugates, we chose the least-efficient serotype in the current pneumococcal conjugate vaccine Prevnar 13, Streptococcus pneumoniae serotype 3 (ST3). Glycan arrays containing synthetic ST3 repeating unit oligosaccharides were used to screen a human reference serum for antibodies and to define the recognition site of two ST3-specific protective monoclonal antibodies. The glycan array screens identified a tetrasaccharide that was selected for in-depth immunological evaluation. The tetrasaccharide-CRM197 carrier protein conjugate elicited protective immunity as evidenced by opsonophagocytosis assays and protection against pneumonia caused by ST3 in mice. Formulation of the defined protective lead candidate glycotope has to be further evaluated to elicit optimal long-term immunity.

Original languageEnglish (US)
Pages (from-to)1407-1416
Number of pages10
JournalCell Chemical Biology
Volume23
Issue number11
DOIs
StatePublished - Nov 17 2016

Keywords

  • Epitope mapping
  • Glycan arrays
  • Glycoconjugate vaccines
  • Opsonophagocytosis
  • Streptococcus pneumoniae
  • Synthetic glycans

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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  • Cite this

    Parameswarappa, S. G., Reppe, K., Geissner, A., Ménová, P., Govindan, S., Calow, A. D. J., Wahlbrink, A., Weishaupt, M. W., Monnanda, B. P., Bell, R. L., Pirofski, L. A., Suttorp, N., Sander, L. E., Witzenrath, M., Pereira, C. L., Anish, C., & Seeberger, P. H. (2016). A Semi-synthetic Oligosaccharide Conjugate Vaccine Candidate Confers Protection against Streptococcus pneumoniae Serotype 3 Infection. Cell Chemical Biology, 23(11), 1407-1416. https://doi.org/10.1016/j.chembiol.2016.09.016