Cholera vaccine

Abstract

Vibrio cholerae, Ogawa serotype, El Tor biotype, are subjected to the mutagenic N-methyl-N'-nitro-n-nitrosoguanidine (NTG). First generation mutants are screened for toxin production, and in particular the absence of "A" or enzymatically active subunit production and production of B (binding) subunit. Putative A.sup.- B.sup.+ mutants are again exposed to NTG and screened for the A.sup.- B.sup.+ characteristics. The formula of the native toxin molecule is usually A.sup.+ B.sup.+.sub.5-6, the formula for the molecule produced by the selected second generation mutant is A.sup.- B.sup.+.sub.5-6. This mutant strain is used for production of a live attenuated vaccine which can be administered orally. The mutant has been found to induce immunity, in an experimental model system, against subsequent challenge with virulent cholera vibrios. Because of the immunologic relationship to other enterotoxins (such as the heat-labile enterotoxin of Escherichia coli), the mutant may also induce immunity to diarrheal diseases other than cholera. In fact, antiserum to the isolated toxin-related protein produced by the mutant has been shown to neutralize E. coli entero-toxin. The mutant may also be used for the production of "choleragenoid", the non-toxic, highly immunogenic B portion of the cholera enterotoxin (choleragen) without the complication of toxicity associated with the complete enterotoxin.

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