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Cholera toxin B subunit

Vaxjo ID 12
Vaccine Adjuvant Name Cholera toxin B subunit
Alternative Names CTB
Adjuvant VO ID VO_0001242
Description Cholera toxin is a potent oral mucosal adjuvant for enteric immunization. Several studies suggest that commercial cholera toxin B subunit (cCTB; purified from holotoxin) may be an effective non-toxic alternative for oral immunization (Blanchard et al., 1998).
Stage of Development Clinical Trial
Components Lyophilized powder containing Tris buffer salts, sodium chloride, sodium azide, and sodium EDTA (Sigma Aldrich).
Dosage Mice were immunized by an intranasal inoculation of 10 µl phosphate-buffered saline (PBS) containing the required dose of CTB (or CT) (Tamura et al., 1988).
Function Cholera toxin and its B subunit are known to bind to the GMl ganglioside found in cell membranes. It has been postulated that this ability confers upon them their mucosal immunogenicity, by aiding uptake by M cells or by trapping mucosal lymphocytes or macrophages or both (McKenzie and Halsey, 1984).
Safety Cholera toxin (CT), produced by Vibrio cholerae, and Escherichia coli heat-labile enterotoxin (LT) whose sequence shows 80% similarity with that of CT are the causative agents of cholera and one of the causative agents of traveller’s diarrhea, respectively (Hagiwara et al., 1999). Although cholera toxin functions as a mucosal adjuvant, its usage as an adjuvant of mucosal vaccine in humans is not feasible owing to its toxicity. In addition, these toxins have another potential drawback, possibly inducing IgE antibody (Ab) responses to bystander antigens, as well as the toxins. These two problems, which impinge on the safety, toxicity and allergenicity of these toxins, should be considered when these toxins are used as a mucosal vaccine adjuvant in humans. One approach being explored to resolve the problems is to use the nontoxic B subunits (CTB or LTB) alone, or B subunits coupled chemically or by gene fusion technology to vaccines. Another approach is to use the B subunits containing a trace amount of the toxin, because the B subunit and a trace amount of the holotoxin act synergistically as an adjuvant for the mucosal immune responses to the vaccine (Hagiwara et al., 1999).
Related Vaccine(s)
References
Blanchard et al., 1998: Blanchard TG, Lycke N, Czinn SJ, Nedrud JG. Recombinant cholera toxin B subunit is not an effective mucosal adjuvant for oral immunization of mice against Helicobacter felis. Immunology. 1998; 94(1); 22-27. [PubMed: 9708182].
Hagiwara et al., 1999: Hagiwara Y, Komase K, Chen Z, Matsuo K, Suzuki Y, Aizawa C, Kurata T, Tamura S. Mutants of cholera toxin as an effective and safe adjuvant for nasal influenza vaccine. Vaccine. 1999; 17(22); 2918-2926. [PubMed: 10438064].
McKenzie and Halsey, 1984: McKenzie SJ, Halsey JF. Cholera toxin B subunit as a carrier protein to stimulate a mucosal immune response. Journal of immunology (Baltimore, Md. : 1950). 1984; 133(4); 1818-1824. [PubMed: 6470484].
Sigma Aldrich: Cholera Toxin B subunit [http://www.sigmaaldrich.com/catalog/ProductDetail.do?D7=0&N5=SEARCH_CONCAT_PNO%7CBRAND_KEY&N4=C1655%7CSIGMA&N25=0&QS=ON&F=SPEC]
Tamura et al., 1988: Tamura S, Samegai Y, Kurata H, Nagamine T, Aizawa C, Kurata T. Protection against influenza virus infection by vaccine inoculated intranasally with cholera toxin B subunit. Vaccine. 1988; 6(5); 409-413. [PubMed: 2848377].