Simultaneous expression of CFA/I and CS3 colonization factor antigens of enterotoxigenic Escherichia coli by delta aroC, delta aroD Salmonella typhi vaccine strain CVD 908.

Among the known colonization factors of enterotoxigenic Escherichia coli (ETEC), CFA/I and CS3 (the common antigen in the CFA/II family of fimbrial antigens) are two of the most prevalent fimbrial antigens found in clinical isolates but are never expressed by the same wild-type strain. We manipulated the genetic determinants encoding CS3 and CFA/I fimbriae so that these two important colonization factors are expressed simultaneously in attenuated Salmonella typhi live oral vaccine strain CVD 908, including after growth in liquid medium (CFA/I is poorly expressed by wild-type ETEC in broth culture). The recombinant fimbrial structures produced by CVD 908 are morphologically indistinguishable from the CS3 fibrillae and CFA/I rod-like fimbriae produced by ETEC, and are recognized by monospecific CS3 and CFA/I antibodies. This prototype construct may prove useful in investigating the live vector approach to immunoprophylaxis of ETEC diarrheal disease.