Unknown

Dataset Information

0

Development of an Efficacious, Semisynthetic Glycoconjugate Vaccine Candidate against Streptococcus pneumoniae Serotype 1.


ABSTRACT: Infections with Streptococcus pneumoniae are a major health burden. Glycoconjugate vaccines based on capsular polysaccharides (CPSs) successfully protect from infection, but not all pneumococcal serotypes are covered with equal potency. Marketed glycoconjugate vaccines induce low levels of functional antibodies against the highly invasive serotype 1 (ST1), presumably due to the obscuring of protective epitopes during chemical activation and conjugation to carrier proteins. Synthetic oligosaccharide antigens can be designed to carry linkers for site-selective protein conjugation while keeping protective epitopes intact. Here, we developed an efficacious semisynthetic ST1 glycoconjugate vaccine candidate. A panel of synthetic oligosaccharides served to reveal a critical role of the rare aminosugar, 2-acetamido-4-amino-2,4,6-trideoxy-d-galactose (d-AAT), for ST1 immune recognition. A monovalent ST1 trisaccharide carrying d-AAT at the nonreducing end induced a strong antibacterial immune response in rabbits and outperformed the ST1 component of the multivalent blockbuster vaccine Prevenar 13, paving the way for a more efficacious vaccine.

SUBMITTER: Schumann B 

PROVIDER: S-EPMC5879475 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

altmetric image

Publications

Development of an Efficacious, Semisynthetic Glycoconjugate Vaccine Candidate against <i>Streptococcus pneumoniae</i> Serotype 1.

Schumann Benjamin B   Reppe Katrin K   Kaplonek Paulina P   Wahlbrink Annette A   Anish Chakkumkal C   Witzenrath Martin M   Pereira Claney L CL   Seeberger Peter H PH  

ACS central science 20180314 3


Infections with <i>Streptococcus pneumoniae</i> are a major health burden. Glycoconjugate vaccines based on capsular polysaccharides (CPSs) successfully protect from infection, but not all pneumococcal serotypes are covered with equal potency. Marketed glycoconjugate vaccines induce low levels of functional antibodies against the highly invasive serotype 1 (ST1), presumably due to the obscuring of protective epitopes during chemical activation and conjugation to carrier proteins. Synthetic oligo  ...[more]

Similar Datasets

| S-EPMC5651752 | biostudies-literature
| S-EPMC5573155 | biostudies-literature
| S-EPMC7506939 | biostudies-literature
| S-EPMC5234679 | biostudies-literature
| S-EPMC4936365 | biostudies-literature
| S-EPMC9930592 | biostudies-literature
| S-EPMC5819008 | biostudies-literature
| S-EPMC10749580 | biostudies-literature
| S-EPMC7349896 | biostudies-literature
| S-EPMC8715227 | biostudies-literature