Characterization and immunogenicity of a Shigella flexneri 2a O-antigen bioconjugate vaccine candidate.

Autor:	Ravenscroft N; Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa., Braun M; LimmaTech Biologics AG, Grabenstrasse 3, 8952 Schlieren, Switzerland., Schneider J; LimmaTech Biologics AG, Grabenstrasse 3, 8952 Schlieren, Switzerland., Dreyer AM; LimmaTech Biologics AG, Grabenstrasse 3, 8952 Schlieren, Switzerland., Wetter M; LimmaTech Biologics AG, Grabenstrasse 3, 8952 Schlieren, Switzerland., Haeuptle MA; LimmaTech Biologics AG, Grabenstrasse 3, 8952 Schlieren, Switzerland., Kemmler S; LimmaTech Biologics AG, Grabenstrasse 3, 8952 Schlieren, Switzerland., Steffen M; LimmaTech Biologics AG, Grabenstrasse 3, 8952 Schlieren, Switzerland., Sirena D; LimmaTech Biologics AG, Grabenstrasse 3, 8952 Schlieren, Switzerland., Herwig S; LimmaTech Biologics AG, Grabenstrasse 3, 8952 Schlieren, Switzerland., Carranza P; LimmaTech Biologics AG, Grabenstrasse 3, 8952 Schlieren, Switzerland., Jones C; Department of Paediatrics, University of Oxford, Oxford OX3 9DU, United Kingdom., Pollard AJ; Department of Paediatrics, University of Oxford, Oxford OX3 9DU, United Kingdom., Wacker M; LimmaTech Biologics AG, Grabenstrasse 3, 8952 Schlieren, Switzerland.; Wacker Biotech Consulting AG, Obere Hönggerstrasse 9a, 8103 Unterengstringen, Switzerland., Kowarik M; LimmaTech Biologics AG, Grabenstrasse 3, 8952 Schlieren, Switzerland.
Jazyk:	angličtina
Zdroj:	Glycobiology [Glycobiology] 2019 Aug 20; Vol. 29 (9), pp. 669-680.
DOI:	10.1093/glycob/cwz044
Abstrakt:	Shigellosis remains a major cause of diarrheal disease in developing countries and causes substantial morbidity and mortality in children. Vaccination represents a promising preventive measure to fight the burden of the disease, but despite enormous efforts, an efficacious vaccine is not available to date. The use of an innovative biosynthetic Escherichia coli glycosylation system substantially simplifies the production of a multivalent conjugate vaccine to prevent shigellosis. This bioconjugation approach has been used to produce the Shigella dysenteriae type O1 conjugate that has been successfully tested in a phase I clinical study in humans. In this report, we describe a similar approach for the production of an additional serotype required for a broadly protective shigellosis vaccine candidate. The Shigella flexneri 2a O-polysaccharide is conjugated to introduced asparagine residues of the carrier protein exotoxin A (EPA) from Pseudomonas aeruginosa by co-expression with the PglB oligosaccharyltransferase. The bioconjugate was purified, characterized using physicochemical methods and subjected to preclinical evaluation in rats. The bioconjugate elicited functional antibodies as shown by a bactericidal assay for S. flexneri 2a. This study confirms the applicability of bioconjugation for the S. flexneri 2a O-antigen, which provides an intrinsic advantage over chemical conjugates due to the simplicity of a single production step and ease of characterization of the homogenous monomeric conjugate formed. In addition, it shows that bioconjugates are able to raise functional antibodies against the polysaccharide antigen. (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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