Cholera Adjuvant

Cholera toxin and related toxins act as immune modulators, with potential use as adjuvants and as therapeutic agents in the treatment of immunologically mediated human disease. 

Holmgren, J., N. Lycke, C. Czerkinsky, Cholera-Toxin and Cholera-B Subunit as Oral Mucosal Adjuvant and Antigen Vector Systems, Vaccine. 11, 1179, 1993. 

The most potent mucosal adjuvants have been shown to be the toxins derived from Vibrio cholerae or Escherichia coli, which should not be surprising since these organisms invade the body through the GI tract. Obviously too toxic for human use because they are the source of cholera or diarrhoea, heat labile enterotoxins have been tested in mice and shown to be potent adjuvants for orally or nasally administered influenza vaccine. The potency of heat-labile enterotoxin mutants may also be enhanced by formulation into bioadhesive particulate delivery systems, and this is an area under current exploration. 

Gagliardi MC, Sallusto F, Marinaro M, Vendetti S, Riccomi A, De Magistris MT Effects of the adjuvant cholera toxin on dendritic cells Stimulatory and inhibitory signals that result in the amplification of immune responses. Int J Med Microbiol 2002 291 571-575. 

Route of exposure—oral/gavage/i.p./others 0 Use of adjuvant—cholera toxin/alum 0 Test material—whole foods/purified proteins 0 Dose frequency—e.g., daily, twice weekly, weekly 0 Dose amount—high dose (tolerance )/low dose(sensitization)... 

The mucosal vaccines approved for human use include typhoid, cholera, adenovirus, Sabin oral polio, and rotavirus vaccines. New mucosal vaccine strategies are focused on development of non-replicating subunit vaccines, DNA, plant, and other types of recombinant vaccines as well as the use of mucosal adjuvants preferably inbuilt into the vaccine. The conjugation of lipids to peptide antigens is one approach which enables the production of highly... 

A cholera vaccine, comprising killed Vibrio cholerae cells and the recombinant cholera toxin B (CTB) subunit (the CTB subunit is used extensively as an adjuvant in mucosal immunization protocols, as it... 

Mineral Salts Immunostimulatory adjuvants Lipid particles Particulate adjuvants Mucosal adjuvants Aluminium hydroxide, aluminium phosphate, calcium phosphate Saponins (e.g., QS21), MDP derivatives, bacterial DNA (CpG oligos), LPS, MPL and synthetic derivatives, lipopeptides, cytokines (e.g., GM-CSF, IL-2, IL-12) Liposomes, virosomes, iscoms, cochleates, emulsions (e.g., Freunds adjuvant, SAF, MF59 ) Poloxamer particles, virus-like particles, PLG microparticles Cholera toxin (CT), mutant toxin (e.g., LTK63, LTR72), heat labile enterotoxin (LT), microparticles, polymerized liposomes, chitosan... 

Hagiwara, Y., Komase, K., Chen, Z., Matsuo, K., Suzuki, Y., Aizawa, C., Kurata, T., and Tamura, S. (1999), Mutants of cholera toxin as an effective and safe adjuvant for nasal influenza vaccine, Vaccine, 17, 2918-2926. 

Homquist, E. Lycke, N. Czerkinsky, C. Holmgren, J. Cholera toxin and cholera B subunit as oral-mucosal adjuvant and antigen carrier systems. In Novel Delivery Systems for Oral Vaccines O Hagan, D.T., Ed. CRC Press, Inc. Ann Arbor, MI, 1994 157-173. 

Scharton-Kersten, T.M. Glenn, G. Vassell, R. Yu, J. Walwender, D. Alving, C.R. Principles of transcutaneous immunization using cholera toxin as an adjuvant. Vaccine, Suppl 17 1999, 2, s37 3. 

Dertzbaugh MT, Elson CO, (1991) Cholera toxin as a mucosal adjuvant. In Topics in Vaccine Adjuvant Research, (Spriggs D, Koff W) CRC Press, Boca Raton, FL,119—132. 

Holmgren J, Czerkinsky C, Lycke N, et al. (1994) Strategies for the induction of immune responses at mucosal surfaces making use of cholera toxin B subunit as immunogen, carrier, and adjuvant. In Am. J. Trop. Med. Hyg. 50 42-54. 

Bacterial toxins As an example, cholera toxin is a strong mucosal adjuvant which can act as adjuvant. 

Cholera toxin (including the nontoxic B chain, CTB) is a potent immune response adjuvant, and fusion of antigens to CTB enhances the binding and effectiveness of antigens. An insulin-CTB fusion protein produced from bacteria has proved difficult to purify, however potato-based expression of such a fusion protein has been successful and oral administration shown to reduce inflammation of the pancreas in diabetic mice [75],... 

Vajdy M, Lyckc NY. Cholera toxin adjuvant promotes long-term immunological memory in the gut mucosa to unrelated immunogens after oral immunization. Immunology 1992 75(3) 488-492. 

Wilson AD, Bailey M, Williams NA et al. Ihe in vitro production of cytokines by mucosal lymphocytes immunized by oral administration of keyhole limpet hemocyanin using cholera toxin as an adjuvant. Eur J Immunol 1991 21(10) 2333-2339. 

Agren LC, Ekman L, Lowcnadler B ct aL Genetically engineered nontoxic vaccine adjuvant that combines B-cell taigedng with immunomodulation by cholera toxin A1 snbnnit. J Immunol 1997 l58(8) 3936-3946. 

Lycke N, Tsuji T, Holmgren J. The adjuvant effect of vibrio cholerae and Escherichia coli heat-labile en-terotoxins is linked to their ADP-ribosyltransfcrase activity. Eur J Immunol 1992 22(9) 2277-2281. 

Millar DG, Hirst TR, Snider DP. Escherichia coli heat-labile enterotoxin B subunit is a more potent mucosal adjuvant than its viosely related homologue, the B subunit of cholera toxin. Infect Immun 2001 69(5) 3476-3482. 

Maeyama J, Isaka M, Yasuda Y et al. Cytokine responses to recombinant cholera toxin B subunit produced by bacillus brevis as a mucosal adjuvant. Microbiol Immunol 2001 45(2) 111-117. 

The capacity of adjuvants to stimulate cytokine production by APCs is important for the initiation of the immune response. As indicated above, ISCOMs induce inflammatory cytokines such as IL-1 and IL-6 from macrophages or monocytes. Compared with adjuvants known as IL-1 inducers, the formulation denominated QH-7.0.3 flu-ISCOMs was as efficient as the most potent IL-1 inducer, i.e. lipopolysaccharide (LPS) and superior to cholera toxin and muramyldipeptide [46]. Furthermore, flu-Ag in ISCOMs-primed T cells had the capacity to secrete high concentrations of IL-2 and IFNy after antigen stimulation in vitro. 

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