Cholera Toxin and its Subunits as Potential Oral Adjuvants

Elson, Charles O.

doi:10.1007/978-3-642-74529-4_3

Cited by 61 publications

(46 citation statements)

References 24 publications

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“…CT has long been shown to promote the development of both humoral and cell-mediated immune responses against several pathogens in mucosal compartments (1,9,10). The most recent evidence for this activity in the field of candidiasis has been provided by Cardenas-Freytag et al (2), who showed the effectiveness of an i.n.-delivered vaccine consisting of whole inactivated Candida cells and a CT-like mucosal adjuvant in conferring protection from a systemic fungus challenge.…”

Section: Vol 70 2002 Notes 2727mentioning

confidence: 99%

“…It is well known that the modalities of antigen administration and the type of adjuvant exert a critical role in the induction of protection, a notation of particular importance for a multifaceted, multiorgan disease such as candidiasis in normal or immunocompromised patients (2,17). Several microbial toxins, among which are the cholera toxin (CT) produced by Vibrio cholerae, and nontoxic derivatives from this and other microorganisms have shown a great potential as mucosal adjuvants for local and systemic antibody responses (9,10,22). Considering that all previous evidence of antibody protective responses at the vaginal level were obtained by local immunization (4-7), while there would be several advantages in immunizing at a nonvaginal mucosal site, we have now compared intranasal to intravaginal immunization with soluble Candida antigens and CT as a mucosal adjuvant for induction of a specific antibody response at the vaginal level and outcome of vaginal infection by C. albicans.…”

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Intravaginal and Intranasal Immunizations Are Equally Effective in Inducing Vaginal Antibodies and Conferring Protection against Vaginal Candidiasis

et al. 2002

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Oophorectomized, estrogen-treated rats were immunized by the intravaginal or intranasal route with a mannoprotein extract (MP) or secreted aspartyl proteinases (Sap) of Candida albicans, with or without cholera toxin as a mucosal adjuvant. Both routes of immunization were equally effective in (i) inducing anti-MP and anti-Sap vaginal antibodies and (ii) conferring a high degree of protection against the vaginal infection by the fungus. These data suggest that appropriate fungal antigens and adjuvant can be used to protect against candidal vaginitis, by either route.

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Section: Vol 70 2002 Notes 2727mentioning

confidence: 99%

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confidence: 99%

Intravaginal and Intranasal Immunizations Are Equally Effective in Inducing Vaginal Antibodies and Conferring Protection against Vaginal Candidiasis

et al. 2002

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“…A major limiting factor for the development of mucosal or transcutaneous vaccines is the availability of safe, effective adjuvants that function non-parenterally and that can initiate and support the transition from innate to adaptive immunity. While a number of substances of bacterial origin have been tested as mucosal or transcutaneous adjuvants, the three bacterial products with the greatest potential to function as non-parenteral adjuvants are the ADP-ribosylating enterotoxins (cholera toxin (CT), produced by various strains of Vibrio cholerae, and the heat-labile enterotoxin (LT) produced by some enterotoxigenic strains of Escherichia coli [1][2][3][4][5]), synthetic oligodeoxynucleotides containing unmethylated CpG dinucleotides (CpG ODN) [6], and monophosphoryl lipid A (MPL) [7][8][9].…”

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confidence: 99%

Effect of adjuvants and route of immunizations on the immune response to recombinant plague antigens

Uddowla

Freytag

Clements

2007

Vaccine

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In this study, we compare four different adjuvants, LT(R192G), CpG ODN, MPL ® TDM and alum, for their ability to affect the magnitude, distribution, and duration of antibody responses against F1-V, the lead-candidate antigen for the next generation vaccine against plague, in a murine model. In addition, three different routes of immunization -intranasal (IN), transcutaneous (TC), and subcutaneous (SC), were compared with each adjuvant. Since aerosol exposure to biological warfare agents is of primary concern, both serum and bronchioalveolar lavage (BAL) were analyzed for antigen-specific antibody responses. The most significant findings of the study reported here are that 1) the adjuvant influences the Type 1/Type 2 balance of the antibody response in both the serum and BAL, 2) mucosal immunization is not necessary to obtain F1-V-specific BAL responses, 3) nontraditional adjuvants such as LT(R192G) work when delivered SC, 4) the route of immunization affects the magnitude of the immune response, and 5) F1-V is highly immunogenic by some routes even in the absence of an exogenously applied adjuvant. These studies provide important insights into the influence of different classes of adjuvants on the immune outcome in biodefense vaccines and for development of new generation vaccines against other pathogens as well.

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“…The B pentamer mediates binding of LT-IIa, LT-IIb, CT, and LT-I to gangliosides, a heterogeneous family of glycolipids located on the surface of mammalian cells (56). CT and LT-I bind with high affinity to GM1 and with lower affinity to ganglioside GD1b; LT-IIa binds specifically, in descending order of avidity, to gangliosides GD1b, GM1, GT1b, GQ1b, GD2, GD1a, and GM3; LT-IIb binds most avidly to GD1a and binds to GM2 and GM3 with much lower affinities (15).LT-IIa, LT-IIb, CT, and LT-I are potent mucosal and systemic adjuvants capable of eliciting strong immune responses to themselves and to unrelated coadministered antigens (8,13,33,34,48,57). Use of these enterotoxins as mucosal adjuvants in human vaccines has been inhibited by their toxic activity.…”

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confidence: 99%

“…LT-IIa, LT-IIb, CT, and LT-I are potent mucosal and systemic adjuvants capable of eliciting strong immune responses to themselves and to unrelated coadministered antigens (8,13,33,34,48,57). Use of these enterotoxins as mucosal adjuvants in human vaccines has been inhibited by their toxic activity.…”

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Mucosal Adjuvant Properties of Mutant LT-IIa and LT-IIb Enterotoxins That Exhibit Altered Ganglioside-Binding Activities

et al. 2005

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Mucosal surfaces represent the major entry route of many microbial pathogens. Hence, it is important that prospective vaccines stimulate maximal immune response at these sites. The mucosal immune system usually requires the aid of immune-stimulating agents (i.e., adjuvants) to generate robust immunity and long-lived memory responses to an antigen. The type I heat-labile enterotoxins produced by Vibrio cholerae and Escherichia coli (CT and LT-I, respectively) have been extensively characterized as mucosal adjuvants in a variety of animals (22). Recently, the immunomodulatory activities of a second class of heat-labile enterotoxins of E. coli were described. This second class consists of LT-IIa and LT-IIb, two heat-labile enterotoxins which can be distinguished from LT-I by a variety of antigenic and genetic differences (17,18). Murine experiments demonstrated that certain immunomodulatory activities of LT-IIa and LT-IIb are equivalent to or greater than those of CT (8, 33).LT-IIa, LT-IIb, CT, and LT-I belong to the AB 5 superfamily of bacterial enterotoxins. Members of this superfamily are related in structure and function (17,18,58,60). Each of these enterotoxins is an oligomeric protein composed of an A polypeptide which is noncovalently coupled to a pentameric array of B polypeptides. The A polypeptide is enzymatically active and upregulates adenylyl cyclase by catalyzing the ADP-ribosylation of the G s␣ regulatory protein. This modification of G s␣ promotes accumulation of intracellular adenosine 3Ј,5Ј cyclic monophosphate (cAMP), which indirectly induces the intoxicated cell to secrete chloride ions and likely modulates other processes for which cAMP is a signaling molecule (4,23,(35)(36)(37). The B pentamer mediates binding of LT-IIa, LT-IIb, CT, and LT-I to gangliosides, a heterogeneous family of glycolipids located on the surface of mammalian cells (56). CT and LT-I bind with high affinity to GM1 and with lower affinity to ganglioside GD1b; LT-IIa binds specifically, in descending order of avidity, to gangliosides GD1b, GM1, GT1b, GQ1b, GD2, GD1a, and GM3; LT-IIb binds most avidly to GD1a and binds to GM2 and GM3 with much lower affinities (15).LT-IIa, LT-IIb, CT, and LT-I are potent mucosal and systemic adjuvants capable of eliciting strong immune responses to themselves and to unrelated coadministered antigens (8,13,33,34,48,57). Use of these enterotoxins as mucosal adjuvants in human vaccines has been inhibited by their toxic activity. Several strategies have been developed to reduce or eliminate the intrinsic toxicity of the type I enterotoxins to facilitate their use as human adjuvants. In early attempts, recombinant B pentamers, due to the absence of the A polypeptide, were used as potential adjuvants. Results of those experiments have been varied, in that the pentamer sometimes potentiated immune responses to a coadministered antigen and at other times was ineffective (1,24,39,64,67). Others have attempted to use recombinant chimeras in which the toxic A polypeptide is genetically replaced with the...

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Cholera Toxin and its Subunits as Potential Oral Adjuvants

Cited by 61 publications

References 24 publications

Intravaginal and Intranasal Immunizations Are Equally Effective in Inducing Vaginal Antibodies and Conferring Protection against Vaginal Candidiasis

Intravaginal and Intranasal Immunizations Are Equally Effective in Inducing Vaginal Antibodies and Conferring Protection against Vaginal Candidiasis

Effect of adjuvants and route of immunizations on the immune response to recombinant plague antigens

Mucosal Adjuvant Properties of Mutant LT-IIa and LT-IIb Enterotoxins That Exhibit Altered Ganglioside-Binding Activities

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