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  A semi-synthetic oligosaccharide conjugate vaccine candidate confers protection against Streptococcus pneumoniae serotype 3 infection

Parameswarappa, S. G., Reppe, K., Geißner, A., Ménová, P., Govindan, S., Calow, A. D. J., et al. (2016). A semi-synthetic oligosaccharide conjugate vaccine candidate confers protection against Streptococcus pneumoniae serotype 3 infection. Cell Chemical Biology, 23(11), 1407-1416. doi:10.1016/j.chembiol.2016.09.016.

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 Creators:
Parameswarappa, Sharavathi Guddehalli1, Author           
Reppe, Katrin, Author
Geißner, Andreas2, Author           
Ménová, Petra1, Author           
Govindan, Subramanian1, Author           
Calow, Adam D. J.1, Author           
Wahlbrink, Annette3, Author           
Weishaupt, Markus W.4, Author           
Monnanda, Bopanna Ponnappa2, Author           
Bell, Roland Lawrence, Author
Pirofski, Liise-Anne, Author
Suttorp, Norbert, Author
Sander, Leif Erik, Author
Witzenrath, Martin, Author
Pereira, Claney Lebev1, Author           
Chakkumkal, Anish2, Author           
Seeberger, Peter H.1, 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              
3Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863286              
4Peter H. Seeberger - Automated Systems, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863306              

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Free keywords: Streptococcus pneumoniae; Synthetic glycans; Glycan arrays; Glycoconjugate vaccines; Epitope mapping; Opsonophagocytosis
 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.

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 Dates: 2016-11-032016
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1016/j.chembiol.2016.09.016
BibTex Citekey: Parameswarappa2016
 Degree: -

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Project name : Automated synthesis of S. pneumoniae 7F capsular polysaccharide repeating unit as candidate for conjugate vaccines
Grant ID : -
Funding program : H2020-EU.1.3.2. (652745)
Funding organization : European Commission (EC)

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Title: Cell Chemical Biology
Source Genre: Journal
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Publ. Info: Cambridge, Massachusetts : Cell Press
Pages: - Volume / Issue: 23 (11) Sequence Number: - Start / End Page: 1407 - 1416 Identifier: ISSN: 2451-9456