After natural infection by V. cholerae, circulating antibodies can be detected against several cholera antigens including the toxin, somatic (O) antigens, and flagellar (H) antigens. These antibodies are also raised by parenteral injection of antigens as vaccine components. Antibodies directed against Vibrio O antigens are considered "vibriocidal" antibodies because they will lyse V. cholerae cells in the presence of complement and serum components. Vibriocidal antibodies reach a peak 8-10 days after the onset of clinical illness, and then decrease, returning to the baseline 2 - 7 months later. Their presence correlates with resistance to infection, but they may not be the mediators of this protection, and the role of circulating antibodies in natural infection is unclear.

After natural infection, people also develop toxin-neutralizing antibodies butthere is no correlation between antitoxic antibody levels and the incidence of disease in cholera zones.

Since cholera is essentially a topical disease of the small intestine, it would seem that topical defense might be a main determinant of protection against infection by V. cholerae. Recurrent infections of cholera are in fact, rare, and this is probably due to local immune defense mediated by antibodies secreted onto the surfaces of the intestinal mucosa. Moreover, in children who are nursing cholera is less likely to occur, presumably due to protection afforded by secretory antibody in mother's milk.

Secretory IgA, as well as IgG and IgM in serum exudate, can be detected in the intestinal mucosa of immune individuals. Although these antibodies presumably have to function in the absence of complement they still bring about protective immunity. Motility is important in pathogenesis, and antibodies against flagella could immobilize the vibrios. Antibodies against flagella or somatic O antigens could cause clumping and arrested motion of cells. Antitoxic antibodies could react with toxin at the epithelial cell surface and block binding or activity of the the toxin.  Since the process by which the vibrios attach to the intestinal epithelium is highly specific, antibodies against Vibrio fimbriae or other surface components (LPS?) could block attachment.

The observation that natural infection confers effective and long-lasting immunity against cholera has led to efforts to develop a vaccine which will elicit protective immunity. The first attempts at a vaccine in 1960s were directed at whole cell preparations injected parenterally. At best, 90% protection was achieved and this immunity waned rapidly to the baseline within one year. Purified LPS fractions from different biotypes have also been given as vaccines with variable success. The cholera toxin can be converted to toxoid in the presence of formalin and glutaraldehyde. The toxoid is a poor antigen, however, and it elicits a very low level of protection.

At the present time, the manufacture and sale of the only licensed cholera vaccine in the United States has been discontinued. Two recently developed oral vaccines for cholera are licensed and available in other countries (Dukoral®, Biotec AB and Mutacol®, Berna). Both vaccines appear to provide  somewhat better immunity and fewer side-effects than the previously available vaccine. However, neither of these two vaccines is recommended for travelers nor are they available in the United States.  Nor are the vaccines recommended for inhabitants of regions where cholera is entrenched, since their use may render complacency with regard to individual susceptibility to disease. One of the vaccines also advertises protection against enterotoxigenic E. coli (ETEC) which produces a toxin (LT) identical to cholera toxin, and which is an important cause of traveller's diarrhea.

The oral vaccines are made from a live attenuated strains of V. cholerae.The ideal properties of such a "vaccine strain" of the bacterium would be to possess all the pathogenicity factors required for colonization of the small intestine (e.g. motility, fimbriae, neuraminidase, etc.) but not to produce a complete toxin molecule. Ideally it should produce only the B subunit of the toxin which would stimulate formation of antibodies that could neutralize the binding of the native toxin molecule to epithelial cells.

A new vaccine has been developed to combat the Vibrio cholerae Bengal strain that has started spreading in epidemic fashion in the Indian subcontinent and Southeast Asia. The Bengal strain differs from previously isolated epidemic strains in that it is serogroup 0139 rather than 01, and it expresses a distinct polysaccharide capsule. Since previous exposure to 01 Vibrio cholerae does not provide protective immunity against 0139, there is no residual immunity in the indigenous population to the Bengal form of cholera.

The noncellular vaccine is relatively nontoxic and contains little or no LPS and other impurities. The vaccine will be used for active immunization against Vibrio cholerae O139 and other bacterial species expressing similar surface polysaccharides. In addition, human or other antibodies induced by this vaccine could be used to identify Vibrio cholerae Bengal for the diagnosis of the infection and for environmental monitoring of the bacterium.

Cholera References and Links

Baron Medical Microbiology Textbook
Cholera, Vibrio cholerae O1 and O139, and Other Pathogenic Vibrios by Richard A. Finkelstein

World Health Organization
Cholera

CDC
Cholera
Travelers' Health Information on Cholera

FDA Bad Bug Book
Vibrio cholerae Serogroup O1