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Semisynthetic glycoconjugate vaccine candidate against Streptococcus pneumoniae serotype 5

MPS-Authors

Lisboa,  Marilda P.
Peter H. Seeberger - Vaccine Development, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Khan,  Naeem
Peter H. Seeberger - Vaccine Development, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Martin,  Christopher
Peter H. Seeberger - Vaccine Development, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Xu,  Fei-Fei
Peter H. Seeberger - Vaccine Development, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Geissner,  Andreas
Chakkumal Anish, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Govindan,  Subramanian
Peter H. Seeberger - Vaccine Development, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Pereira,  Claney L.
Peter H. Seeberger - Vaccine Development, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Seeberger,  Peter H.
Peter H. Seeberger - Vaccine Development, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Citation

Lisboa, M. P., Khan, N., Martin, C., Xu, F.-F., Reppe, K., Geissner, A., et al. (2017). Semisynthetic glycoconjugate vaccine candidate against Streptococcus pneumoniae serotype 5. Proceedings of the National Academy of Sciences of the United States of America, 114(42), 11063-11068. doi:10.1073/pnas.1706875114.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002E-08FE-F
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.