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Cell Chem Biol. 2016 Nov 17;23(11):1407-1416. doi: 10.1016/j.chembiol.2016.09.016. Epub 2016 Nov 3.

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

Author information

1
Department of Biomolecular Systems, Max-Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany.
2
Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany.
3
Department of Biomolecular Systems, Max-Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany; Institute of Chemistry and Biochemistry, Freie Universität Berlin, Arnimallee 22, 14195 Berlin, Germany.
4
Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY 10461, USA; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
5
Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany. Electronic address: martin.witzenrath@charite.de.
6
Department of Biomolecular Systems, Max-Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany; Institute of Chemistry and Biochemistry, Freie Universität Berlin, Arnimallee 22, 14195 Berlin, Germany. Electronic address: peter.seeberger@mpikg.mpg.de.

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

PMID:
27818299
PMCID:
PMC5234679
DOI:
10.1016/j.chembiol.2016.09.016
[Indexed for MEDLINE]
Free PMC Article

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