Development of a Vaccine Against Experimental Cholera and Escherichia coli Diarrheal Disease

Abstract

The results of the present investigation indicate a simple approach to the development of a single-vaccine formula which may ultimately be used to confer protection against both cholera and certain types of Escherichia coli diarrheal disease in humans and domestic animals. The design of the vaccine is based on the well-documented ability of cholera antitoxin to neutralize both cholera and heat-labile E. coli enterotoxins (CT and LT, respectively) and on the ability of killed E. coli to enhance the immune response to cholera toxoid and, possibly, to conventional cholera vaccine as well. Evidence presented shows that a parenterally administered E. coli vaccine, prepared from an LT-only enterotoxigenic strain, reproducibly elevated rabbit antitoxin responses to cholera toxoid and that such responses correlated with dramatic protection against live cholera vibrios and the homologous E. coli strain in the rabbit ligated loop model of diarrheal disease. The results show also that cholera vaccine acted to suppress the rabbits' immune response to the cholera toxoid and E. coli vaccine formula, even though all three antigens combined still provided significant protection against live organism challenge. On the basis of data presently available, the vaccine formula would be composed simply of cholera toxoid and E. coli vaccine, but may also include cholera vaccine. Since it has already been established that cholera toxoid and cholera vaccine are each safe for human use, additional vaccine development would require investigation of the safety of E. coli vaccine, alone and in combination with the other components.