English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  A semisynthetic Streptococcus pneumoniae serotype 8 glycoconjugate vaccine

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

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-2BA3-E Version Permalink: http://hdl.handle.net/21.11116/0000-0006-5EBB-F
Genre: Journal Article

Files

show Files
hide Files
:
2407259.pdf (Publisher version), 7MB
 
File Permalink:
-
Name:
2407259.pdf
Description:
-
Visibility:
Restricted (Max Planck Institute of Colloids and Interfaces, MTKG; )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
2407259_supp.pdf (Supplementary material), 20MB
 
File Permalink:
-
Name:
2407259_supp.pdf
Description:
-
Visibility:
Restricted (Max Planck Institute of Colloids and Interfaces, MTKG; )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show

Creators

show
hide
 Creators:
Schumann, Benjamin1, Author              
Hahm, Heung Sik2, Author              
Parameswarappa, Sharavathi Guddehalli3, Author              
Reppe, Katrin, Author
Wahlbrink, Annette1, Author              
Govindan, Subramanian3, Author              
Kaplonek, Paulina1, Author              
Pirofski, Liise-anne, Author
Witzenrath, Martin, Author
Chakkumkal, Anish4, Author              
Pereira, Claney L.3, Author              
Seeberger, Peter H.3, Author              
Affiliations:
1Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863286              
2Peter H. Seeberger - Automated Systems, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863306              
3Peter H. Seeberger - Vaccine Development, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863308              
4Chakkumal Anish, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863299              

Content

show
hide
Free keywords: -
 Abstract: Pediatric vaccines targeting bacterial capsular polysaccharides are more effective for certain types of bugs than others, and the manufacturing process as well as immunodominance of different glycan epitopes (glycotopes) can lead to a mixed immune response that does not protect against disease. To directly identify glycotopes that induce a protective response, Schumann et al. combined antibody reverse engineering with automated glycan assembly using Streptococcus pneumoniae serotype 8 as a proof of concept. Promising glycotopes conjugated to a carrier protein induced protective antibodies in mice and were also immunogenic in rabbits. When combined with a commercially available pneumococcal vaccine, these glycoconjugates were able to boost the opsonophagocytic bacterial killing ability of sera from immunized rabbits. This approach leveraging semisynthetic glycoconjugates could lead to the design of more effective bacterial vaccines.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 frameshifts 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.

Details

show
hide
Language(s):
 Dates: 2017
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1126/scitranslmed.aaf5347
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Science Translational Medicine
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Washington, DC : AAAS
Pages: - Volume / Issue: 9 (380) Sequence Number: eaaf5347 Start / End Page: - Identifier: ISSN: 1946-6234