Adjuvant activity of Escherichia coli heat-labile enterotoxin and effect on the induction of oral tolerance in mice to unrelated protein antigens

Clements, John D.; Hartzog, Nancy M.; Lyon, Frank L.

doi:10.1016/0264-410x(88)90223-x

Cited by 273 publications

(151 citation statements)

References 28 publications

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“…Both CT and Escherichia coli heat-labile enterotoxin (LT) are potent oral antigens and, in addition, provide adjuvant activity to antigens that are coadministered with them orally (13,14). Because the responses to potato HBsAg were much lower in the absence of CT, it is possible that an effective mucosal adjuvant will be needed for orally delivered material in human subjects.…”

Section: Discussionmentioning

confidence: 99%

Oral immunization with hepatitis B surface antigen expressed in transgenic plants

Kong

Richter

Yang

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

288

196

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Oral immunogenicity of recombinant hepatitis B surface antigen (HBsAg) derived from yeast (purified product) or in transgenic potatoes (uncooked unprocessed sample) was compared. An oral adjuvant, cholera toxin, was used to increase immune responses. Transgenic plant material containing HBsAg was the superior means of both inducing a primary immune response and priming the mice to respond to a subsequent parenteral injection of HBsAg. Electron microscopy of transgenic plant samples revealed evidence that the HBsAg accumulated intracellularly; we conclude that natural bioencapsulation of the antigen may provide protection from degradation in the digestive tract until plant cell degradation occurs near an immune effector site in the gut. The correlate of protection from hepatitis B virus infection is serum antibody titers induced by vaccination; the protective level in humans is 10 milliunits͞ml or greater. Mice fed HBsAg-transgenic potatoes produced HBsAg-specific serum antibodies that exceeded the protective level and, on parenteral boosting, generated a strong longlasting secondary antibody response. We have also shown the effectiveness of oral delivery by using a parenteral prime-oral boost immunization schedule. The demonstrated success of oral immunization for hepatitis B virus with an ''edible vaccine'' provides a strategy for contributing a means to achieve global immunization for hepatitis B prevention and eradication.

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Section: Discussionmentioning

confidence: 99%

Oral immunization with hepatitis B surface antigen expressed in transgenic plants

Kong

Richter

Yang

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

288

196

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“…In addition, both toxins can act as adjuvants for the enhancement of mucosal and serum antibody responses to a mucosal co-administered antigen, resulting in a long-term memory to this antigen [35,105,202]. The immune response that is occurring against these toxins is not an advantage.…”

Section: Cholera Toxin and Escherichia Coli Thermolabile Enterotoxinmentioning

confidence: 99%

Adjuvants modulating mucosal immune responses or directing systemic responses towards the mucosa

et al. 2006

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-In developing veterinary mucosal vaccines and vaccination strategies, mucosal adjuvants are one of the key players for inducing protective immune responses. Most of the mucosal adjuvants seem to exert their effect via binding to a receptor/or target cells and these properties were used to classify the mucosal adjuvants reviewed in the present paper: (1) ganglioside receptor-binding toxins (cholera toxin, LT enterotoxin, their B subunits and mutants); (2) surface immunoglobulin binding complex CTA1-DD; (3) TLR4 binding lipopolysaccharide; (4) TLR2-binding muramyl dipeptide; (5) Mannose receptor-binding mannan; (6) Dectin-1-binding ß 1,3/1,6 glucans; (7) TLR9-binding CpG-oligodeoxynucleotides; (8) Cytokines and chemokines; (9) Antigen-presenting cell targeting ISCOMATRIX and ISCOM. In addition, attention is given to two adjuvants able to prime the mucosal immune system following a systemic immunization, namely 1α, 25(OH) 2 D 3 and cholera toxin.

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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].…”

Section: Introductionmentioning

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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Adjuvant activity of Escherichia coli heat-labile enterotoxin and effect on the induction of oral tolerance in mice to unrelated protein antigens

Cited by 273 publications

References 28 publications

Oral immunization with hepatitis B surface antigen expressed in transgenic plants

Oral immunization with hepatitis B surface antigen expressed in transgenic plants

Adjuvants modulating mucosal immune responses or directing systemic responses towards the mucosa

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

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