Genetics of cholera toxin.

Cholera is caused by the toxin secreted by Vibrio cholerae 01. Cholera toxin (CT) is a protein consisting of A and B subunits. The former contributes to intracellular toxicity whereas the B subunit is required for binding of CT to eukaryotic cell surface receptor. The structural genes encoding A and B subunits are designated as ctxA and ctxB respectively. These genes are located on the chromosome forming an operon in which ctxA precedes ctxB. The ctxAB have been cloned and sequenced. Classical strains contain two full copies of unlinked ctxAB. Most el tors have single copy. However, in some strains there are two copies which are arranged in tandem. The tandem duplication and amplification of ctxAB is controlled by a transposable element like DNA sequence called RS1. A number of genes have been identified which regulate the expression of ctx operon. V. cholerae seems to elaborate more than one toxin which are different from the one encoded by ctxAB genes.

The current status of cholera vaccine development and experience with cholera vaccine trials in volunteers.

In recent years notable advances have been made in the development of improved vaccines to prevent cholera. These new vaccines are administered orally to maximally stimulate intestinal secretory immunity. Killed vibrios, given in conjunction with purified B subunit or administered alone, in three spaced doses, caused no adverse reactions and have conferred significant protection in volunteer challenge studies and in field trials. Two attenuated mutants of V. cholerae, prepared by recombinant DNA techniques, CVD 103 and CVD 103-HgR are well-tolerated and elicit prominent immune responses and protective immunity after ingestion of a single oral dose. Other modern approaches being pursued include the development of auxotrophic strains and of modifying attenuated S. typhi strain Ty21a to express V. cholerae Inaba and Ogawa LPS antigens.