Mucosal adjuvanticity and immunogenicity of LTR72, a novel mutant of Escherichia coli heat-labile enterotoxin with partial knockout of ADP- ribosyltransferase activity

Journal of Experimental Medicine

Volumn 187, Issue 7, 1998, Pages 1123-1132

  Giuliani, Marzia Monica ^a   Del Giudice, Giuseppe ^a   Giannelli, Valentina ^a   Dougan, Gordon ^b   Douce, Gill ^b   Rappuoli, Rino ^a   Pizza, Mariagrazia ^a  

^a CHIRON VACCINES   (Italy)

^b IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE; ARGININE; ESCHERICHIA COLI ENTEROTOXIN; IMMUNOGLOBULIN; IMMUNOGLOBULIN A; IMMUNOGLOBULIN G; IMMUNOLOGICAL ADJUVANT; MUTANT PROTEIN; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; OVALBUMIN;

ADENOSINE DIPHOSPHATE RIBOSYLATION; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTIBODY RESPONSE; ARTICLE; CONTROLLED STUDY; ENZYME ACTIVITY; FEMALE; ILEUM; IMMUNIZATION; IMMUNOGENICITY; LYMPHOCYTE PROLIFERATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; RABBIT; T LYMPHOCYTE;

ADJUVANTS, IMMUNOLOGIC; ADMINISTRATION, INTRANASAL; ANIMALS; ENTEROTOXINS; ENZYME STABILITY; ESCHERICHIA COLI; IMMUNOGLOBULIN G; INTESTINES; MICE; MUTAGENESIS, SITE-DIRECTED; OVALBUMIN; POLY(ADP-RIBOSE) POLYMERASES; RABBITS; T-LYMPHOCYTES;

EID: 0032489830     PISSN: 00221007     EISSN: None     Source Type: Journal    
DOI: 10.1084/jem.187.7.1123     Document Type: Article

References (58)

1. Spangler, B.D. 1992. The heat-labile enterotoxin of E. coli. Microbiol. Rev. 56:622-647.
2. Mekalanos, J.J., D.J. Swartz, G.D. Pearson, N. Harford, F. Groyne, and M. Je Wilde, 1983. Cholera toxin genes: nucleotide sequence, deletion analysis and vaccine development. Nature. 306:551-557.
3. Dallas, W.S., and S. Falkow. 1980. Amino acid homology between cholera toxin and Escherichia coli heat labile toxin. Nature. 288:499-501.
4. Spicer, E.K., W.M. Kavanaugh, W.S. Dallas, S. Falkow, W.H. Konigsberg, and D. Shafer. 1981. Sequence homologies between A subunits of E. coli and V. cholerae enterotoxins. Proc. Natl. Acad. Sci. USA. 78:50-54.
5. Sixma, T.K., S.E. Pronk, K.H. Kalk, E.S. Wartna, B.A. van Zanten, B. Witholt, and W.G. Hol. 1991. Crystal structure of a cholera toxin-related heat-labile enterotoxin from E. coli. Nature. 351:371-377.
6. Holmgren, J. 1981. Actions of cholera toxin and the prevention and treatment of cholera. Nature. 292:413-417.
7. 32P]ADP-ribosylation of proteins. Methods Enzymol. 195:267-280.
8. Moss, J., and M. Vaughan. 1988. ADP-ribosylation of guanyl nucleotide-binding regulatory proteins by bacterial toxins. Adv. Enzymol. Relat. Areas Mol. Biol. 61:303-379.
9. Sugii, S.T. 1989. Binding specificities of heat-labile enterotoxins isolated from porcine and human enterotoxigenic Escherichia coli for different gangliosides. Can. J. Microbiol. 35: 670-673.
10. Holmgren, J., I. Lonnroth, and L. Svennerholm. 1973. Tissue receptor for cholera exotoxin: postulated structure from studies with GM1-ganglioside and related glycolipids. Infect. Immun. 8:208-214.
11. Rappuoli, R., and Pizza, M. 1991. Structure and evolutionary aspects of ADP-ribosylating toxins. In Sourcebook of Bacterial Protein Toxins. J. Alouf and J. Freer, editors. Academic Press, New York. p. 1-20
12. Moss, J., and M. Vaughan. 1984. Toxin ADP-ribosyltransferases that act on adenylato-cyclase systems. Methods Enzymol. 106:411-418.
13. Field, M., M.C. Rao, and E.B. Chang. 1989. Intestinal electrolyte transport and diarrheal disease. N. Engl. J. Med. 321: 800-806.
14. Clements, J.D., R.J. Yancy, and R.A. Finkelstein. 1980. Properties of homogeneous heat-labile enterotoxin from E. coli. Infect. Immun. 29:91-97.
15. Jackson, R.J., K. Fujihashi, J. Xu Amano, H. Kiyono, C.O. Ekon, and J.R. McGhee. 1993. Optimizing oral vaccines: induction of systemic and mucosal B-cell and antibody responses to tetanus toxoid by use of cholera toxin as an adjuvant. Infect. Immun. 61:4272-4279.
16. Debard, N., D. Buzoni Gatel, and D. Bout. 1996. Intranasal immunization with SAG1 protein of Toxoplasma gondii in association with cholera toxin dramatically reduces development of cerebral cystis after oral infection. Infect. Immun. 64: 2158-2166.
17. Marchetti, M., B. Arico, D. Burroni, N. Figura, R. Rappuoli, and P. Ghiara. 1995. Development of a mouse model of Helicobacter pylori infection that mimics human disease. Science. 267:1655-1658.
18. Rollwagen, F.M., N.D. Pacheco, J.D. Clements, O. Pavlovskis, D.M. Rollins, and R.I. Walker. 1993. Killed Campylobacter elicits immune response and protection when administered with an oral adjuvant. Vaccine. 11:1316-1320.
19. Levine, M.M., J.B. Kaper, R.E. Black, and M.L. Clements. 1983. New knowledge on pathogenesis of bacterial enteric infections as applied to vaccine development. Microbiol. Rev. 47:510-550.
20. Holmgren, J., A.M. Svennerholm, M. Jertborn, J. Clemens, D.A. Sack, R. Salenstedt, and H. Wigzell. 1992. An oral B subunit: whole cell vaccine against cholera. Vaccine. 10:911-914.
21. Tamura, S., H. Funato, T. Nagamine, C. Aizawa, and T. Kurata. 1989. Effectiveness ot cholera toxin B subunit as an adjuvant for nasal influenza vaccination despite pre-existing immunity to CTB. Vaccine. 7:503-505.
22. Pizza, M., M. Domenighini, W. Hol, V. Giannelli, M.R. Fontana, M.M. Giuliani, C. Magagnoh, S. Peppoloni, R. Manetti, and R. Rappuoli. 1994. Probing the structure-activity relationship of Escherichia coli LT-A by site-directed mutagenesis. Mol. Microbiol. 14:51-60.
23. De Haan, L., W.R. Verweij, I.K. Feil, T.H. Lijnema, W.G. Hol, E. Agsteribbe, and J. Wilschut. 1996. Mutants of Eicherichia coli heat-labile enterotoxin with reduced ADP-ribosylation activity or no activity retain the immunogenic properties of the native holotoxin. Infect. Immun. 64:5413-5416.
24. Fontana, M.R., R. Manetti, V. Giannelli, C. Magagnoli, A. Marchini, M. Domenighini, R. Rappuoli, and M. Pizza. 1995. Construction of non toxic derivatives of cholera toxin and characterization of the immunological response against the A subunit. Infect. Immun. 63:2356-2360.
25. Yamamoto, S., H. Kiyono, M. Yamamoto, K. Imaoka, M. Yamamoto, K. Fujihashi, F.W. Van Ginkel, M. Noda, Y. Takeda, and J.R. McGhee. 1997. A non toxic mutant of cholera toxin elicits Th2-type responses for enhanced mucosal immunity. Proc. Natl. Acad. Sci. USA. 94:5267-5272.
26. Nashar, T.O., H.M. Webb, S. Eaglestone, N.A. Williams, and T.R. Hirst. 1996. Potent immunogenicity of the B subunits of Escherichia coli heat labile enterotoxin: receptor binding is essential and induces differential modulation of lymphocyte subsets. Proc. Natl. Acad. Sci. USA. 93:226-230.
27. Pizza, M., M.R. Fontana, M.M. Giuliani, M. Domenighini, C. Magagnoli, V. Giannelli, D. Nucci, W. Hol, R. Manetti, and R. Rappuoli. 1994. A genetically detoxified derivative of heat-labile E. coli enterotoxin induces neutralizing antibodies against the A subunit. J. Exp. Med. 6:2147-2153.
28. Magagnoli, C., R. Manetti, M.R. Fontana, V. Giannelli, M.M. Giuliani, R. Rappuoli, and M. Pizza. 1996. Mutations in the A subunit affect yield, stability, and protease sensivity of nontoxic derivatives of heat-labile enterotoxin. Infect. Immun. 64:5434-5438.
29. Wilson, A.D., A. Robinson, L. Irons, and C.R. Stokes. 1993. Adjuvant action of cholera toxin and pertussis toxin in the induction of IgA antibody response to orally administered antigen. Vaccine. 11:113-118.
30. Lycke, N., T. Tsuji, and J. Holmgren. 1992. The adjuvant effect of Vibrio cholerae and Escherichia coli heat-labile enterotoxins is linked to their ADP-ribosyltransferase activity. Eur. J. Immunol. 22:2277-2281.
31. Clements, J.D., N.M. Hartzog, and F.L. Lyon. 1988. Adjuvant activity of Escherichia coli heat-labile enterotoxin and effect on the induction of oral tolerance in mice to unrelated protein antigens. Vaccine. 6:269-277.
32. Douce, G., C. Turcotte, I. Cropley, M. Roberts, M. Pizza, M. Domenghini, R. Rappuoli, and G. Dougan. 1995. Mutants of Escherichia coli heat-labile toxin lacking ADP-ribosyltransferase activity act as nontoxic, mucosal adjuvants. Proc. Natl. Acad. Sci. USA. 92:1644-1648.
33. Di Tommaso, A., G. Saletti, M. Pizza, R. Rappuoli, G. Dougan, S. Abrignani, G. Douce, and M.T. De Magistris. 1996. Induction of antigen-specific antibodies in vaginal secretions by using a nontoxic mutant of heat-labile enterotoxin as a mucosal adjuvant. Infect. Immun. 64:974-979.
34. Douce, G., M.R. Fontana, M. Pizza, R. Rappuoli, and G. Dougan. 1997. Intranasal immunogenicity and adjuvanticity of site directed mutant derivatives of Cholera toxin. Infect. Immun. 65:2821-2828.
35. Partidos, C.D., M. Pizza, R. Rappuoli, and M.W. Steward. 1996. The adjuvant effect of a non-toxic mutant of heat-labile enterotoxin of Escherichia coli for the induction of measles virus-specific CTL responses after intranasal co-immunization with a synthetic peptide. Immunology. 89:483-487.
36. Marchetti, M., M. Rossi, V. Giannelli, M.M. Giuliani, M. Pizza, S. Censini, A. Covacci, P. Massari, C. Pagliaccia, R. Manetti, et al. 1998. Protection against Helicobacter pylori infection in mice by intragastric vaccination with H. pylori antigens is achieved using a non-toxic mutant of E.coli heat-labile enterotoxin (LT) as adjuvant. Vaccine. 16:33-37.
37. Ghiara, P., M. Rossi, M. Marchetti, A. Di Tommaso, C. Vindigni, F. Ciampolini, A. Covacci, J.L. Telford, M.T. De Magistris, M. Pizza, et al. 1997. Therapeutic intragastric vaccination against Helicobacter pylori in mice eradicates an otherwise chronic infection and confers protection against reinfection. Infect. Immun. 65:4996-5002.
38. Sixma, T.K., K.H. Kalk, B.A. Vanzanten, Z. Dauter, J. Kingma, B. Witholt, and W.G. Hol. 1993. Refined structure of Escherichia cell heat-labile enterotoxin, a close relative of Cholera toxin. J. Mol. Biol. 230:890-918.
39. Zoller, M.J., and M. Smith. 1982. Oligonucleotide-directed mutagenesis using M13-derived vectors: an efficient and general procedure for the production of point mutations in any fragment of DNA. Nucleic Acids Res. 10:6487-6500.
40. Sambrook, J., E.F. Fritsch, and T. Maniatis. 1989. Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
41. Pronk, S.E., H. Hofstra, H. Groendijk, J. Kingma, M.B.A. Swarte, F. Dorner, J. Drenth, W. Hol, and B. Witholt. 1985. Heat-labile enterotoxin of Escherichia coli: characterization of different crystal forms. J. Biol. Chem. 260:13580-13584.
42. Lai, C., F. Cancedda, and L.K. Duffy. 1981. ADP-ribosyltranferase activity of Cholera toxin polypeptide A1 and the effect of limited trypsinolysis. Biochem. Biophys. Res. Commun. 102:1021-1027.
43. Donta, S.T., H.W. Moon, and S.C. Whipp. 1973. Detection and use of heat-labile Escherichia coli enterotoxin with the use of adrenal cells in tissue culture. Science. 183:334-335.
44. De, S.N. 1959. Enterotoxicity of bacteria-free culture filtrate of Vibrio cholerae. Nature. 183:1533-1534.
45. Domenighini, M., C. Magagnoli, M. Pizza, and R. Rappuoli. 1994. Common features of the NAD-binding and catalytic site of ADP-ribosylating toxins. Mol. Microbiol. 14:41-50.
46. Giannelli, V., M.R. Fontana, M.M. Giuliani., D. Guancai, R. Rappuoli, and M. Pizza 1997. Protease susceptibility and toxicity of heat-labile enterotoxins with a mutation in the active site or in the protease-sensitive loop. Infect. Immun. 65: 331-334.
47. Tamura, S., A. Yamanaka, M. Shimohara, T. Tomita, K. Komase, Y. Tsuda, Y. Suzuki, T. Nagamine, K. Kawahara, H. Danbara, et al., 1994. Synergistic action of cholera toxin B subunit (and Escherichia coli heat-labile toxin B subunit) and a trace amount of cholera whole toxin as an adjuvant for nasal influenza vaccine. Vaccine. 12:419-426.
48. Dickison, B.L., and J.D. Clements. 1995. Dissociation of Escherichia coli heat-labile enterotoxin adjuvanticity from ADP-rybosyltranferase activity. Infect. Immun. 63:1617-1623.
49. Grant, C.R., R.J. Messer, and W.J. Cieplack. 1994. Role of trypsin-like cleavage at arginine 192 in the enzymatic and cytotonic activities of Escherichia coli heat-labile enterotoxin. Infect. Immun. 62:4270-4278.
50. Bergquist, C., E.L. Johansonn, T. Lagergard, J. Holmgren, and A. Rudin. 1997. Intranasal vaccination of humans with recombinant cholera toxin B subunit induces systemic and local antibody responses in the upper respiratory tract and the vagina. Infect. Immun. 65:2676-2684.
51. Conference Coverage (ICAAC). 1997. New mucosal adjuvant safe in humans. Vaccine Weekly. November 3.4.
52. Agren, L.C., L. Ekman, B. Lowenadler, and N.Y. Lycke. 1997. Genetically engineered nontoxic vaccine adjuvant that combines B cell targeting with immunomodulation by cholera toxin A1 subunit. J. Immunol. 158:3936-3946.
53. Bromander, A., J. Holmgren, and N. Lycke. 1991. Cholera toxin stimulates IL-1 production and enhances antigen presentation by macrophages in vitro. J. Immunol. 146:2908-2914.
54. McGhee, D.W., C.O. Elson, and J.R. McGhee. 1993. Enhancing effect of cholera toxin on Interleukin-6 secretion by IEC-6 intestinal epithelial cells: mode of action and augmenting effect of inflammatory cytokines. Infect. Immun. 61:4637-4644.
55. Takahashi, I., M. Marinaro, H. Kiyono, R.J. Jackson, I. Nakagawa, K. Fujihashi, S. Hamada, J.D. Clements, K.L. Bost, and J.R. McGhee. 1996. Mechanisms for mucosal immunogenicity and adjuvancy of Escherichia coli labile enterotoxin. J. Infect. Dis. 173:627-635.
56. Douce, G., M.M. Giuliani, V. Giannelli, M. Pizza, R. Rappuoli, and G. Douga. 1998. Mucosal immunogenicity of genetically detoxified derivatives of heat labile toxin from Escherichia coli. Vaccine. In press.
57. Dragunsky, E.M., E. Rivera, W. Aaronson, T.M. Dolgaya, H.D. Hochstein, W.H. Habig, and I.S. Levenbook. 1992. Experimental evaluation of antitoxic protective effect of new cholera vaccines in mice. Vaccine. 10:735-736.
58. Richardson, S.H., and R.E. Kuhn. 1986. Studies on the genetic and cellular control of sensitivity enterotoxins in the sealed adult mouse model. Infect. Immun. 54:522-528.