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

doi:10.1016/j.chembiol.2016.09.016

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

Medicine

Research output: Contribution to journal › Article › peer-review

50 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 language	English (US)
Pages (from-to)	1407-1416
Number of pages	10
Journal	Cell Chemical Biology
Volume	23
Issue number	11
DOIs	https://doi.org/10.1016/j.chembiol.2016.09.016
State	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.chembiol.2016.09.016

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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

Parameswarappa, SG, Reppe, K, Geissner, A, Ménová, P, Govindan, S, Calow, ADJ, Wahlbrink, A, Weishaupt, MW, Monnanda, BP, Bell, RL, Pirofski, LA, Suttorp, N, Sander, LE, Witzenrath, M, Pereira, CL, Anish, C & Seeberger, PH 2016, 'A Semi-synthetic Oligosaccharide Conjugate Vaccine Candidate Confers Protection against Streptococcus pneumoniae Serotype 3 Infection', Cell Chemical Biology, vol. 23, no. 11, pp. 1407-1416. https://doi.org/10.1016/j.chembiol.2016.09.016

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

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.",

keywords = "Epitope mapping, Glycan arrays, Glycoconjugate vaccines, Opsonophagocytosis, Streptococcus pneumoniae, Synthetic glycans",

author = "Parameswarappa, {Sharavathi Guddehalli} and Katrin Reppe and Andreas Geissner and Petra M{\'e}nov{\'a} and Subramanian Govindan and Calow, {Adam D.J.} and Annette Wahlbrink and Weishaupt, {Markus W.} and Monnanda, {Bopanna Ponnappa} and Bell, {Roland Lawrence} and Pirofski, {Liise Anne} and Norbert Suttorp and Sander, {Leif Erik} and Martin Witzenrath and Pereira, {Claney Lebev} and Chakkumkal Anish and Seeberger, {Peter H.}",

note = "Funding Information: This work was supported in part by the Max Planck Society (to P.H.S.), the German Research Council (DFG), the Collaborative Research Centre SFB-TR 84 (C3, C6 to M.W.; C8 to L.E.S. and P.H.S.; B1 to N.S.; SA1940/2-1 to L.E.S.), by the German Ministry for Education and Research (e:Med CAPSyS, TP2 to N.S.; TP4 to M.W.) and the United States National Institutes of Health (NIH) to L.P. ( R56AI104234 and R01AG045044 ). P.M. acknowledges support by a European Research Council fellowship (Marie Sklodowska-Curie Actions project no. 652745). The authors gratefully thank Sven Hammerschmidt for kindly providing S. pneumoniae serotype 3 (NCTC7978) and Uwe Vogel for the valuable technical supervision of flow cytometry. The excellent technical assistance of Maria Spelling and Denise Barthel is greatly appreciated. Parts of this work will be included in the doctoral theses of R.L.B. and A.G. P.H.S. is a shareholder of Vaxxilon AG, Reinach, Switzerland. S.G.P. and C.L.P. are employees of a Vaxxilon AG subsidiary. Publisher Copyright: {\textcopyright} 2016 Elsevier Ltd",

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AU - Parameswarappa, Sharavathi Guddehalli

AU - Reppe, Katrin

AU - Geissner, Andreas

AU - Ménová, Petra

AU - Govindan, Subramanian

AU - Calow, Adam D.J.

AU - Wahlbrink, Annette

AU - Weishaupt, Markus W.

AU - Monnanda, Bopanna Ponnappa

AU - Bell, Roland Lawrence

AU - Pirofski, Liise Anne

AU - Suttorp, Norbert

AU - Sander, Leif Erik

AU - Witzenrath, Martin

AU - Pereira, Claney Lebev

AU - Anish, Chakkumkal

AU - Seeberger, Peter H.

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N2 - 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.

AB - 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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KW - Glycan arrays

KW - Glycoconjugate vaccines

KW - Opsonophagocytosis

KW - Streptococcus pneumoniae

KW - Synthetic glycans

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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