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Because a large portion of the enterotoxigenic E. coli that cause disease produce only ST, attempts have been made to immunize against this toxin, despite its poor immunogenicity. Encouraging results were obtained by conjugating ST to porcine IgG. Subsequently, a bivalent toxoid was prepared by cross-linking ST to LT. Testing of a bivalent toxoid consisting of a laboratory-synthesized ST conjugated to the B subunit also has begun. Both of these bivalent toxoids have demonstrated immunogenicity and protective effects in animal models.

Another approach toward prevention of enterotoxigenic E. coli diarrhea involves the use of attenuated strains of E. coli bearing critical antigens. These strains should be capable of colonizing the small intestine and stimulating an immune response, without causing adverse reactions. One live strain, a CFA II-positive, LT- and ST-negative variant of a previously enterotoxigenic strain, has been evaluated in humans. When given to volunteers, all excreted the strain, most had positive cultures of jejunal fluid, and most had serological responses. About 10 percent of the volunteers developed mild diarrhea, however, presumably as a consequence of colonization of the proximal small intestine.

With the advent of recombinant DNA technology, it is possible to construct an E. coli vaccine strain engineered to produce large quantities of multiple colonization factor antigens, B subunit, and perhaps an ST toxoid. Further work will be necessary to understand, and if possible eliminate, the mild diarrhea resulting from CFA-positive strains of E. coli.

A potential problem with all of the proposed vaccines is that there is no assurance they will provide long-term (up to 5 years) protection. This is an important goal, especially for vaccine use in developing countries.

REFERENCES

Black, R.E. 1984. Personal communication, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Md.


Dupont, H.L. 1982. Escherichia coli diarrhea. Pp. 219–234 in Bacterial Infections of Human, A.S.Evans and H.A.Feldman, eds. New York: Plenum.


Levine, M.L., J.B.Kaper, R.E.Black, and M.L.Clements. 1983. New knowledge on pathogenesis of bacterial enteric infections as applied to vaccine development. Microbiol. Rev. 47:510–550.



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