Toward an effective prophylactic immunity to cholera.

An effective immunity may be considered to be the mirror image of the pathogenesis of the infectious disease against which it is directed and, in general, is dual in nature; i.e., it includes antimicrobial and antitoxic components. In cholera the relative importance of these 2 elements of immunity is not yet defined. It is probable that presently used vaccines, consisting of suspensions of killed vibrios, are effective immunizing agents with respect to the former as evidenced by their ability to protect against challenge infection in mice, to elicit the formation of vibriocidal antibody, and to provide partial limited protection against the naturally occurring disease in man [1]. The toxic element in the pathogenesis of cholera requires more precise definition in that there are at least 5 separable toxic activities formed by the cholera vibrio [2]. Of these, the predominating one is that which induces increased movement of water and ions from the tissues into the lumen of the bowel and is demonstrable in 8 animal models of the disease described to date. The contribution of the other toxic activities to the pathogenesis of the disease is yet uncertain. It may be that delayed death in diarrheal cholera, cholera sicca, certain clinical features of the disease such as loss of potassium, some portion of the observed histopathology, etc., will be found to be attributable to one or another of these other toxins. While definitive evidence is not available, it is considered probable by many workers that present cholera vaccines are deficient with respect to their ability to stimulate the production of toxin-neutralizing antibody. The significance of such antibody in the human infection is indicated by the occurrence of high antitoxic and low vibriocidal serum antibody titers in asymptomatic infections, which has been reported by the author previously and has also been observed by others. While it would seem to be implicit, it may be stated ex