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Proc Natl Acad Sci U S A. 2017 Oct 17;114(42):11063-11068. doi: 10.1073/pnas.1706875114. Epub 2017 Oct 2.

Semisynthetic glycoconjugate vaccine candidate against Streptococcus pneumoniae serotype 5.

Author information

1
Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, D-14424 Potsdam, Germany.
2
Department of Chemistry and Biochemistry, Freie Universität Berlin, D-14195 Berlin, Germany.
3
Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.
4
Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, D-14424 Potsdam, Germany; claney.pereira@vaxxilon.com peter.seeberger@mpikg.mpg.de.

Abstract

Glycoconjugate vaccines based on isolated capsular polysaccharide (CPS) save millions of lives annually by preventing invasive pneumococcal disease caused by Streptococcus pneumoniae Some components of the S. pneumoniae glycoconjugate vaccine Prevnar13 that contains CPS antigens from 13 serotypes undergo modifications or degradation during isolation and conjugation, resulting in production problems and lower efficacy. We illustrate how stable, synthetic oligosaccharide analogs of labile CPS induce a specific protective immune response against native CPS using S. pneumoniae serotype 5 (ST-5), a problematic CPS component of Prevnar13. The rare aminosugar l-PneuNAc and a branched l-FucNAc present in the natural repeating unit (RU) are essential for antibody recognition and avidity. The epitope responsible for specificity differs from the part of the antigen that is stabilized by chemical modification. Glycoconjugates containing stable, monovalent synthetic oligosaccharide analogs of ST-5 CPS RU induced long-term memory and protective immune responses in rabbits superior to those elicited by the ST-5 CPS component in multivalent Prevnar13.

KEYWORDS:

S. pneumoniae; carbohydrate chemistry; glycoconjugate; serotype 5; vaccine

PMID:
28973947
PMCID:
PMC5651752
DOI:
10.1073/pnas.1706875114
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Conflict of interest statement: P.H.S. declares a significant financial interest in Vaxxilon, the company that commercializes the Streptococus pneumoniae vaccine candidate described here. There is, however, no conflict of interest, as this is a purely scientific manuscript that was not sponsored by the company.

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