Pathogenic and vaccine significance of toxin-coregulated pill of Vibrio cholerae El Tor

Vibrio cholerae O1 strains are classified into one of two biotypes, classic al and El Tor, the latter being primarily responsible for cholera cases wor ldwide since 1961. Recent studies in our laboratory have focused upon the p athogenic and vaccine significance of the toxin-coregulated pill (TCP) prod uced by strains of El Tor biotype. Mutants in which the tcpA gene (encoding the pilin subunit protein) has been inactivated are dramatically attenuate d in the infant mouse cholera model, showing markedly reduced colonisation potential in mixed-infection competition experiments. Significantly, in the vaccine context, antibodies to TCP are sufficient to prevent experimental infection, although our data suggest that this protective effect might be l imited to strains of homologous biotype. Since we have shown that tcpA sequ ences are conserved within a biotype but differ between biotypes, this latt er observation suggests that the biotype-restricted pilin epitopes might ha ve greater vaccine significance. Similar studies indicate that TCP also pla y a critical role in colonisation by strains of the recently-recognised O13 9 serogroup, which is thought to have evolved from an O1 El Tor strain. In contrast to the effect of introducing mutations in the tcpA gene, strains c arrying inactivated mshA genes (encoding the subunit of the mannose-sensiti ve haemagglutinin pilus) show unaltered in vivo behaviour. Consistent with this finding is our inability to demonstrate any protective effect associat ed with antibodies to MSHA. Ongoing approaches to vaccine development are v ariously aimed at improving the immunogenicity of the current inactivated w hole-cell vaccine, or assessing the field efficacy of a promising live atte nuated strain. The possible implications of our findings are discussed in r elation to both of these options. (C) 1999 Elsevier Science B.V. All rights reserved.