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  Semisynthetic glycoconjugate vaccine candidate against Streptococcus pneumoniae serotype 5

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.

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Item Permalink: https://hdl.handle.net/11858/00-001M-0000-002E-08FE-F Version Permalink: https://hdl.handle.net/21.11116/0000-0001-3FBF-3
Genre: Journal Article

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 Creators:
Lisboa, Marilda P.1, Author
Khan, Naeem1, Author           
Martin, Christopher1, Author           
Xu, Fei-Fei1, Author           
Reppe, Katrin, Author
Geissner, Andreas2, Author           
Govindan, Subramanian1, Author           
Witzenrath, Martin, Author
Pereira, Claney L.1, Author           
Seeberger, Peter H.3, 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              
3Peter H. Seeberger, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_2040285              

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 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.

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 Dates: 20172017-10-17
 Publication Status: Issued
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 Identifiers: DOI: 10.1073/pnas.1706875114
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Title: Proceedings of the National Academy of Sciences of the United States of America
  Other : Proceedings of the National Academy of Sciences of the USA
  Other : Proc. Acad. Sci. USA
  Other : Proc. Acad. Sci. U.S.A.
  Abbreviation : PNAS
Source Genre: Journal
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Publ. Info: Washington, D.C. : National Academy of Sciences
Pages: - Volume / Issue: 114 (42) Sequence Number: - Start / End Page: 11063 - 11068 Identifier: ISSN: 0027-8424