Cell Chem Biol. 2016 Nov 2. pii: S2451-9456(16)30356-7. doi: 10.1016/j.chembiol.2016.09.016. [Epub ahead of print]

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

Parameswarappa SG1, Reppe K2, Geissner A3, Ménová P1, Govindan S1, Calow AD1, Wahlbrink A1, Weishaupt MW3, Monnanda BP3, Bell RL2, Pirofski LA4, Suttorp N2, Sander LE2, Witzenrath M5, Pereira CL1, Anish C1, Seeberger PH6.

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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.

Copyright © 2016 Elsevier Ltd. All rights reserved.

KEYWORDS:

Epitope mapping; Glycan arrays; Glycoconjugate vaccines; Opsonophagocytosis; Streptococcus pneumoniae; Synthetic glycans

PMID: 27818299 DOI: 10.1016/j.chembiol.2016.09.016

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