Despite more than a century of efforts, an ideal cholera vaccine is still not a reality. We have developed a recombinant live oral attenuated Vibrio cholerae O1 vaccine that provides protective immunity in volunteers from experimental challenge after a single dose and also provides protection in an outbreak situation. The earlier versions of the vaccine were reactogenic in North American volunteers with inflammatory diarrhea, low grade fever and other symptoms noted in approximately 50% of subjects. We have shown that all five of the V. cholerae flagellin proteins induce IL-8 production in a TLR-5 dependent fashion. Although V. cholerae is the prototypic non-inflammatory diarrheal pathogen, we hypothesize that the proinflammatory response due to flagellin in ctx mutant vaccine strains is usually counteracted by anti-inflammatory effects of cholera toxin in wild type strains. To investigate genes and potential antigens that are expressed in vivo during V. cholerae infection, we have conducted a resolvase in vivo expression technology (RIVET) study in volunteers and identified promoters that are specifically induced during infection but not during in vitro growth.
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