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Surface expression of Helicobacter pylori HpaA adhesion antigen on Vibrio cholerae, enhanced by co-expressed enterotoxigenic Escherichia coli fimbrial antigens

Journal article
Authors Joshua Tobias
Michael Lebens
S. N. Wai
Jan Holmgren
Ann-Mari Svennerholm
Published in Microbial Pathogenesis
Volume 105
Pages 177-184
ISSN 0882-4010
Publication year 2017
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Pages 177-184
Language en
Links dx.doi.org/10.1016/j.micpath.2017.0...
Keywords V cholerae, H. pylori, ETEC Heterologous surface expression, Co-expression, COLONIZATION FACTOR CS6, MONOCLONAL-ANTIBODIES, ADULT VOLUNTEERS, GENE-EXPRESSION, H-NS, INFECTION, VACCINES, IDENTIFICATION, CONSTRUCTION, RESPONSES
Subject categories Microbiology in the medical area

Abstract

Helicobacter pylori infection can cause peptic ulceration and is associated with gastric adenocarcinoma. This study aimed to construct and characterize a non-virulent Vibrio cholerae 01 strain, which grows more rapidly than H. pylori, as vector for H. pylori antigens for possible use as a vaccine strain against H. pylori. This was done by recombinant expression of the H. pylori adhesion antigen HpaA alone or, as a proof of principle, together with different colonization factor (CF) antigens of enterotoxigenic Escherichia coli (ETEC) which may enhance immune responses against HpaA. A recombinant V cholerae strain co expressing HpaA and a fimbrial CF antigens CFA/I or CS5, but not the non-fimbrial CF protein CS6, was shown to express larger amounts of HpaA on the surface when compared with the same V cholerae strain expressing HpaA alone. Mutations in the CFA/I operon showed that the chaperon, possibly together with the usher, was involved in enhancing the surface expression of HpaA. Oral immunization of mice with formaldehyde-inactivated recombinant V cholerae expressing HpaA alone or together with CFA/I induced significantly higher serum antibody responses against HpaA than mice similarly immunized with inactivated HpaA-expressing H. pylori bacteria. Our results demonstrate that a non-virulent V cholerae strain can be engineered to allow strong surface expression of HpaA, and that the expression can be further increased by co-expressing it with ETEC fimbrial antigens. Such recombinant V cholerae strains expressing HpaA, and possibly also other H. pylori antigens, may have the potential as oral inactivated vaccine candidates against H. pylori. (C) 2017 Elsevier Ltd. All rights reserved.

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