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October 16, 1987

Attenuated Salmonella Becomes Versatile Vector in Multivalent, Multipurpose Genetic Vaccines

JAMA. 1987;258(15):2028. doi:10.1001/jama.1987.03400150018006

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AN AVIRULENT Salmonella strain is the basis of the first bacterial vaccine to generate a mucosal as well as cellular and humoral immune response.

The vaccine is a genetically engineered form of Salmonella typhi that has been rendered avirulent by removal of the genes that code for two enzymes, adenylate cyclase and C-reactive protein, that are necessary to produce cyclic adenosine monophosphate (cAMP). Robbed of its ability to produce cAMP, the bacterium cannot metabolize sugars, transport amino acids, or synthesize cell-surface structures. It is carried to its customary habitat—the lymphoid cells of the gastrointestinal mucosa or Peyer's patches—where, lacking the capability (and the cilia) to go forth and multiply, it lives for five to seven days.

The odds are heavily against the avirulent Salmonella's reacquiring the ability to make cAMP by picking up a plasmid containing the gene from another gut-dwelling bacterium, says the vaccine's developer, Roy Curtiss