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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

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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]

PMID: 29632881

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Project description:IntroductionStreptococcus pneumoniae is a leading cause of pneumonia among children. However, owing to diagnostic limitations, the protection conferred by pneumococcal conjugate vaccines (PCVs) against pediatric pneumonia attributable to vaccine-serotype pneumococci remains unknown.MethodsWe analyzed data on vaccination and nasopharyngeal pneumococcal detection among children <5 years old with community-acquired alveolar pneumonia (CAAP; "cases") and those without respiratory symptoms ("controls"), who were enrolled in population-based prospective surveillance studies in southern Israel between 2009 and 2018. We measured PCV-conferred protection against carriage of vaccine-serotype pneumococci via the relative risk of detecting these serotypes among vaccinated versus unvaccinated controls. We measured protection against progression of vaccine serotypes from carriage to CAAP via the relative association of vaccine-serotype detection in the nasopharynx with CAAP case status, among vaccinated and unvaccinated children. We measured PCV-conferred protection against CAAP attributable to vaccine-serotype pneumococci via the joint reduction in risks of carriage and disease progression.ResultsOur analyses included 1032 CAAP cases and 7743 controls. At ages 12-35 months, a PCV13 schedule containing 2 primary doses and 1 booster dose provided 87.2% (95% confidence interval: 8.1-100.0%) protection against CAAP attributable to PCV13-serotype pneumococci, and 92.3% (-0.9%, 100.0%) protection against CAAP attributable to PCV7-serotype pneumococci. Protection against PCV13-serotype and PCV7-serotype CAAP was 67.0% (-424.3%, 100.0%) and 67.7% (-1962.9%, 100.0%), respectively, at ages 36-59 months. At ages 4-11 months, 2 PCV13 doses provided 98.9% (-309.8%, 100.0%) and 91.4% (-191.4%, 100.0%) against PCV13-serotype and PCV7-serotype CAAP.ConclusionsAmong children, PCV-conferred protection against CAAP attributable to vaccine-targeted pneumococcal serotypes resembles protection against vaccine-serotype invasive pneumococcal disease.

Dataset Information

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

Publications

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

Similar Datasets

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