A NONTOXIC CHOLERA ENTEROTOXIN (CT) ANALOG IS CHIMERIC WITH REGARD TOBOTH EPITYPES OF CT-B SUBUNITS, CT-B-1 AND CT-B-2

The gene encoding a nontoxic analog, CT-2(), of cholera enterotoxin ( CT) with attenuating codon substitutions in the A subunit was introduc ed into the attenuated Vibrio cholerae classical biotype mutant candid ate vaccine strain CVD103, which produces the B subunit (but not the A subunit) of CT-1. The recombinant strain produces a chimeric nontoxic analog holotoxin protein containing both CT-B-1 and CT-B-2 subunits. This offers potential advantages over CVD103 in the induction of immun ity against El Tor biotype and V. cholerae O139 strains which produce CT-B-2. The recombinant protein may also be useful in polysaccharide-p rotein conjugate vaccines against both O1 and O139 serovars of V. chol erae.