Recombinant Live Cholera Vaccines

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Abstract
This chapter reviews developments and progress in the use of recombinant bacteria as live oral cholera vaccines. The extent to which a prior clinical infection with wild-type enterotoxigenic Vibrio cholerae O1 stimulates protection against cholera in the face of subsequent challenge with wildtype V. cholerae O1 comes from two sources, volunteer studies and epidemiologic studies in endemic areas. The molecular pathogenesis of cholera infection is one of the best-studied bacterial infections and is characterized by cascades of coordinately regulated virulence properties. Vibriocidal antibody is measured by bacterial lysis when serial dilutions of serum are incubated with a large standardized inoculum of V. cholerae O1 in the presence of guinea pig complement. A series of early vaccine candidates was constructed from wild-type V. cholerae strains known to be pathogenic for volunteers by introducing deletions in the chromosomal genes encoding the A (ADP-ribosylating "toxic") subunit or both the A and B (nontoxic binding) subunits of cholera enterotoxin. Investigators at the Center for Vaccine Development of the University of Maryland have identified two new toxins in addition to cholera toxin that are elaborated by virulent V. cholerae O1. The genes that encode these two toxins, zonula occludens toxin (Zot) and accessory cholera toxin (Ace), are located on the "cholera toxin element" of the cholera chromosome contiguous to ctxAB, which encodes cholera toxin. Clinical trials with candidate live oral vaccines against V. cholerae O139 are expected to commence in 1994.