Live bacterial vaccines: environmental aspects.

Recombinant DNA technology has greatly accelerated the development of live attenuated bacterial vaccines for cholera, typhoid, and shigellosis. Significant attenuation has been achieved by deleting genes for various virulence determinants, biosynthetic genes, and regulatory genes. As these vaccine candidates move from closed-ward clinical studies to outpatient and field trials, a variety of concerns needs to be addressed about the safety of these vaccines, not only for the vaccinee, but also for the community and the environment. In the case of Vibrio cholerae, specific deletions (delta attRS1 and delta recA) have been introduced into some live vaccine candidates, rendering them incapable of performing homologous and site-specific recombination events that could lead to reacquisition of active cholera toxin genes. Mutations in recA might also limit the persistence of the live vaccine candidate in the environment.