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Construction of novel vaccine strains of Vibrio cholerae co-expressing the Inaba and Ogawa serotype antigens.

Journal article
Authors Michael Lebens
Stefan Karlsson
Susanne Källgård
Margareta Blomqvist
Annelie Ekman
Erik Nygren
Jan Holmgren
Published in Vaccine
Volume 29
Issue 43
Pages 7505-7513
ISSN 0264-410X
Publication year 2011
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Pages 7505-7513
Language en
Links dx.doi.org/10.1016/j.vaccine.2011.0...
Keywords Cholera; Vaccine; Vibrio cholerae; Serotype; Hikojima; Immunogenicity
Subject categories Industrial Biotechnology

Abstract

The approach of inducing protective immunity against cholera by oral vaccination with killed whole Vibrio cholerae cells is effective, but the complexity of current cholera vaccines makes them difficult and relatively expensive to manufacture, especially if recombinant cholera toxin B subunit is included in the formulation. In an effort to simplify the composition of a new generation of oral cholera vaccines we have generated a novel non-toxigenic candidate vaccine strain of V. cholerae O1 that stably expresses both the Ogawa and Inaba serotype antigens on its surface. This was done by introducing a functional wbeT gene without a functional promoter into the chromosome of an O1 Inaba strain. The resulting low levels of expression of the wbeT gene product allowed for the desired partial serotype switching. This strain (MS1342) can potentially replace the three virulent strains used in currently manufactured cholera vaccines. Oral immunization of mice with formalin-killed MS1342 bacteria gave rise to Ogawa-specific, Inaba-specific and cross-reactive serum antibodies that were detectable both by lipopolysaccharide (LPS)-specific ELISAs and as vibriocidal antibodies that are considered to predict protective efficacy. These responses as well as intestinal mucosal IgA anti-LPS antibody responses were fully comparable with those obtained by immunization with the internationally licensed oral cholera vaccine Dukoral(®). We propose that such a strain may form the basis of a single strain killed whole cell cholera vaccine protecting against cholera caused by either the Inaba or Ogawa serotype of V. cholerae O1.

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