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Chapter 27 : Protective Oral Cholera Vaccine Based on a Combination of Cholera Toxin B Subunit and Inactivated Cholera Vibrios

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Protective Oral Cholera Vaccine Based on a Combination of Cholera Toxin B Subunit and Inactivated Cholera Vibrios, Page 1 of 2

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Abstract:

There is an increasing need for an effective cholera vaccine. Although cholera can be treated successfully by oral and intravenous rehydration and electrolyte replacement therapy, diarrhea treatment centers are still scarce in many areas where cholera is now endemic, and use of an effective vaccine may in many places be the most promising possibility for controlling the disease or at least be a valuable complement to other control strategies. The intense vaccine development and research efforts during the last 10 years have now provided several oral vaccine candidates based on either a combination of nonliving bacteria and purified B-subunit antigen, or on live attenuated mutants of O1 that produce the B subunit. The clarification of the subunit structure of cholera toxin and the roles of different subunits in toxin action immediately suggested a way to prepare a safe and highly immunogenic "toxoid" consisting of the purified cholera B subunits. Studies of the immune mechanisms operating in cholera and the immune response to various cholera antigens, especially cholera toxin and its B-subunit moiety, have been central themes in much of the recent mucosal immunity research. The B-subunit component is completely nontoxic and has proved to be an exceptionally potent oral immunogen because of its stability and its ability to bind to the intestinal mucosa. The results with the oral B-subunit-whole cell vaccine represent marked improvements over those achieved previously with parenteral cholera vaccines.

Citation: Holmgren J, Osek J, Svennerholm A. 1994. Protective Oral Cholera Vaccine Based on a Combination of Cholera Toxin B Subunit and Inactivated Cholera Vibrios, p 415-424. In Wachsmuth I, Blake P, Olsvik Ø (ed), and Cholera. ASM Press, Washington, DC. doi: 10.1128/9781555818364.ch27
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Figures

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Figure 1

Pathogenesis of cholera and main targets of vaccine-induced immune protection. As illustrated, O1 bacteria have special (and apparently in part biotype-specific) means of adhering to, colonizing, and multiplying to large numbers in the small intestine. During these processes, the bacteria produce and release significant amounts of cholera enterotoxin. After binding (by means of the five B subunits) to GM, ganglioside receptors and ADP-ribosylating (ADPR) one of the regulatory subunits (N[G) of adenylate cyclase (by means of the A subunit), cholera toxin stimulates excessive formation in affected enterocytes of cyclic AMP, which in turn through the associated secretion of electrolytes and water into the gut lumen may cause severe diarrhea and dehydration. Protective immunity is mainly mediated by locally produced secretory IgA antibodies interfering with bacterial colonization and/or toxin binding, and the goal of vaccination should be to effectively stimulate these types of antibodies (together with a long-lasting immunologic memory for anamnestic local antibody production).

Citation: Holmgren J, Osek J, Svennerholm A. 1994. Protective Oral Cholera Vaccine Based on a Combination of Cholera Toxin B Subunit and Inactivated Cholera Vibrios, p 415-424. In Wachsmuth I, Blake P, Olsvik Ø (ed), and Cholera. ASM Press, Washington, DC. doi: 10.1128/9781555818364.ch27
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References

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Tables

Generic image for table
Table 1

Composition of B-subunit-whole-cell cholera vaccine

Citation: Holmgren J, Osek J, Svennerholm A. 1994. Protective Oral Cholera Vaccine Based on a Combination of Cholera Toxin B Subunit and Inactivated Cholera Vibrios, p 415-424. In Wachsmuth I, Blake P, Olsvik Ø (ed), and Cholera. ASM Press, Washington, DC. doi: 10.1128/9781555818364.ch27
Generic image for table
Table 2

Results from randomized placebo-controlled field trial of oral B-subunit-whole-cell cholera vaccine and whole-cell vaccine alone given in three (or two) doses

Citation: Holmgren J, Osek J, Svennerholm A. 1994. Protective Oral Cholera Vaccine Based on a Combination of Cholera Toxin B Subunit and Inactivated Cholera Vibrios, p 415-424. In Wachsmuth I, Blake P, Olsvik Ø (ed), and Cholera. ASM Press, Washington, DC. doi: 10.1128/9781555818364.ch27
Generic image for table
Table 3

Biotype-specific protective effect of anti-MSHA and anti-TCP antibodies against El Tor and classical cholera, respectively, in the infant mouse cholera model

Citation: Holmgren J, Osek J, Svennerholm A. 1994. Protective Oral Cholera Vaccine Based on a Combination of Cholera Toxin B Subunit and Inactivated Cholera Vibrios, p 415-424. In Wachsmuth I, Blake P, Olsvik Ø (ed), and Cholera. ASM Press, Washington, DC. doi: 10.1128/9781555818364.ch27

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