A semisynthetic Streptococcus pneumoniae serotype 8 glycoconjugate vaccine

Benjamin Schumann, Heung Sik Hahm, Sharavathi G. Parameswarappa, Katrin Reppe, Annette Wahlbrink, Subramanian Govindan, Paulina Kaplonek, Liise-anne Pirofski, Martin Witzenrath, Chakkumkal Anish, Claney L. Pereira, Peter H. Seeberger

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Glycoconjugate vaccines based on capsular polysaccharides (CPSs) of pathogenic bacteria such as Streptococcus pneumoniae successfully protect from disease but suffer from incomplete coverage, are troublesome to manufacture from isolated CPSs, and lack efficacy against certain serotypes. Defined, synthetic oligosaccharides are an attractive alternative to isolated CPSs but require the identification of immunogenic and protective oligosaccharide antigens. We describe a medicinal chemistry strategy based on a combination of automated glycan assembly (AGA), glycan microarray-based monoclonal antibody (mAb) reverse engineering, and immunological evaluation in vivo to uncover a protective glycan epitope (glycotope) for S. pneumoniae serotype 8 (ST8). All four tetrasaccharide frame-shifts of ST8 CPS were prepared by AGA and used in glycan microarray experiments to identify the glycotopes recognized by antibodies against ST8. One tetrasaccharide frameshift that was preferentially recognized by a protective, CPS-directed mAb was conjugated to the carrier protein CRM197. Immunization of mice with this semisynthetic glycoconjugate followed by generation and characterization of a protective mAb identified protective and nonprotective glycotopes. Immunization of rabbits with semisynthetic ST8 glycoconjugates containing protective glycotopes induced an antibacterial immune response. Coformulation of ST8 glycoconjugates with the marketed 13-valent glycoconjugate vaccine Prevnar 13 yielded a potent 14-valent S. pneumoniae vaccine. Our strategy presents a facile approach to develop efficient semisynthetic glycoconjugate vaccines.

Original languageEnglish (US)
Article numbereaaf5347
JournalScience Translational Medicine
Volume9
Issue number380
DOIs
StatePublished - Mar 8 2017

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Glycoconjugates
Streptococcus pneumoniae
Polysaccharides
Vaccines
Monoclonal Antibodies
Oligosaccharides
Immunization
Serogroup
Synthetic Vaccines
Pharmaceutical Chemistry
Epitopes
Carrier Proteins
Rabbits
Bacteria
Antigens

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Schumann, B., Hahm, H. S., Parameswarappa, S. G., Reppe, K., Wahlbrink, A., Govindan, S., ... Seeberger, P. H. (2017). A semisynthetic Streptococcus pneumoniae serotype 8 glycoconjugate vaccine. Science Translational Medicine, 9(380), [eaaf5347]. https://doi.org/10.1126/scitranslmed.aaf5347

A semisynthetic Streptococcus pneumoniae serotype 8 glycoconjugate vaccine. / Schumann, Benjamin; Hahm, Heung Sik; Parameswarappa, Sharavathi G.; Reppe, Katrin; Wahlbrink, Annette; Govindan, Subramanian; Kaplonek, Paulina; Pirofski, Liise-anne; Witzenrath, Martin; Anish, Chakkumkal; Pereira, Claney L.; Seeberger, Peter H.

In: Science Translational Medicine, Vol. 9, No. 380, eaaf5347, 08.03.2017.

Research output: Contribution to journalArticle

Schumann, B, Hahm, HS, Parameswarappa, SG, Reppe, K, Wahlbrink, A, Govindan, S, Kaplonek, P, Pirofski, L, Witzenrath, M, Anish, C, Pereira, CL & Seeberger, PH 2017, 'A semisynthetic Streptococcus pneumoniae serotype 8 glycoconjugate vaccine', Science Translational Medicine, vol. 9, no. 380, eaaf5347. https://doi.org/10.1126/scitranslmed.aaf5347
Schumann B, Hahm HS, Parameswarappa SG, Reppe K, Wahlbrink A, Govindan S et al. A semisynthetic Streptococcus pneumoniae serotype 8 glycoconjugate vaccine. Science Translational Medicine. 2017 Mar 8;9(380). eaaf5347. https://doi.org/10.1126/scitranslmed.aaf5347
Schumann, Benjamin ; Hahm, Heung Sik ; Parameswarappa, Sharavathi G. ; Reppe, Katrin ; Wahlbrink, Annette ; Govindan, Subramanian ; Kaplonek, Paulina ; Pirofski, Liise-anne ; Witzenrath, Martin ; Anish, Chakkumkal ; Pereira, Claney L. ; Seeberger, Peter H. / A semisynthetic Streptococcus pneumoniae serotype 8 glycoconjugate vaccine. In: Science Translational Medicine. 2017 ; Vol. 9, No. 380.
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