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Development of Stable Vibrio cholerae O1 Hikojima Type Vaccine Strains Co-Expressing the Inaba and Ogawa Lipopolysaccharide Antigens

Journal article
Authors Stefan Karlsson
Elisabeth Ax
Erik Nygren
Susanne Källgård
Margareta Blomquist
Annelie Ekman
John Benktander
Jan Holmgren
Michael Lebens
Published in Plos One
Volume 9
Issue 11
ISSN 1932-6203
Publication year 2014
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Language en
Links dx.doi.org/10.1371/journal.pone.010...
Keywords ESCHERICHIA-COLI, MONOCLONAL-ANTIBODIES, COLONIZATION FACTORS, B-SUBUNIT, BACTERIA, CONSTRUCTION, EFFICACY, CHAIN, ETEC, MICE, Multidisciplinary Sciences, ROEHER UH, 1992, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES, LORENZO V, 1994, BACTERIAL PATHOGENESIS, PT A, V235, P386
Subject categories Clinical Medicine

Abstract

We describe here the development of stable classical and El Tor V. cholerae O1 strains of the Hikojima serotype that co-express the Inaba and Ogawa antigens of O1 lipopolysaccharide (LPS). Mutation of the wbeT gene reduced LPS perosamine methylation and thereby gave only partial transformation into Ogawa LPS on the cell surface. The strains express approximately equal amounts of Inaba- and Ogawa-LPS antigens which are preserved after formalin-inactivation of the bacteria. Oral immunizations of both inbred and outbred mice with formalin-inactivated whole-cell vaccine preparations of these strains elicited strong intestinal IgA anti-LPS as well as serum vibriocidal antibody responses against both Inaba and Ogawa that were fully comparable to the responses induced by the licensed Dukoral vaccine. Passive protection studies in infant mice showed that immune sera raised against either of the novel Hikojima vaccine strains protected baby mice against infection with virulent strains of both serotypes. This study illustrates the power of using genetic manipulation to improve the properties of bacteria strains for use in killed whole-cell vaccines.

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