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Bacterial Toxins as Mucosal Adjuvants

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Defense of Mucosal Surfaces: Pathogenesis, Immunity and Vaccines

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 236))

Abstract

The 1995 World Health Organization report of infectious-disease deaths indicated there had been more than 13 million deaths world-wide during that year. The majority of those deaths were caused by organisms that first make contact with and then either colonize or cross mucosal surfaces to infect the host. The overall morbidity caused by these organisms and other pathogens that interact with mucosal surfaces is impossible to calculate.

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References

  • Bromander AK, Kjerrulf M, Holmgren J, Lycke N (1993) Cholera toxin enhances alloantigen presentation by cultured intestinal epithelial cells. Scand J Immunol 37:452–458

    Article  PubMed  CAS  Google Scholar 

  • Brown W, Woods V, Chitko-McKown C, Hash S, Rice-Ficht A (1994) Interleukin-10 is expressed by bovine type 1 helper, type 2 helper,and unrestricted parasite-specific T-cell clones and inhibits proliferation of all three subsets in an accessory-cell-dependent manner. Infect Immun 62:4697–4708

    PubMed  CAS  Google Scholar 

  • Burnette WN, Mar VL, Platler BW, Schlotterbeck JD, McGinley MD, Stoney KS, Rhode MF, Kaslow HR (1991) Site-specific mutagenesis of the catalytic subunit of cholera toxin: substituting lysine for arginine 7 causes loss of activity. Infect Immun 59:4266–4270

    PubMed  CAS  Google Scholar 

  • Cebra J J, Fuhrman JA, Lebman DA, London SD (1986) Effective gut mucosal stimulation of IgA-committed B cells by antigen. In: Brown F, Channok RM, Lerner RA (eds) Vaccines 86: new approaches to immunization. Developing vaccines against parasitic, bacterial, and viral diseases. Cold Spring Harbor, New York, pp 129–133

    Google Scholar 

  • Cherwinski HM, Schumacher JH, Brown KD, Mosmann TR (1987) Two types of mouse helper T cell clones. J Exp Med 166:1229–1244

    Article  PubMed  CAS  Google Scholar 

  • Chong C, Friberg M, Clements JD (1998) LT(R192G), a non-toxic mutant of the heat-labile enterotoxin of Escherichia coli, elicits enhanced humoral and cellular immune responses associated with protection against lethal oral challenge with Salmonella spp. Vaccine 16:732–740

    Article  PubMed  CAS  Google Scholar 

  • Clarke CJ, Wilson AD, Williams NA, Stokes CR (1991) Mucosal priming of T-lymphocyte responses to fed protein antigens using cholera toxin as an adjuvant. Immunology 72:323–328

    PubMed  CAS  Google Scholar 

  • Clements JD, Hartzog NM, Lyon FL (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

    Article  PubMed  CAS  Google Scholar 

  • Dickinson BL, Clements JD (1995) Dissociation of Escherichia coli heat-labile enterotoxin adjuvanticity from ADP-ribosyltransferase activity. Infect Immun 63:1617–1623

    PubMed  CAS  Google Scholar 

  • DiTommaso A, Saletti G, Pizza M, Rappuoli R, Dougan G, Abrignani S, Douce G, DeMagistris MT (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

    CAS  Google Scholar 

  • Domenighini M, Magagnoli C, Pizza M, Rappuoli R (1994) Common features of the NAD-binding and catalytic site of ADP-ribosylating toxins. Mol Microbiol 14:41–50

    CAS  Google Scholar 

  • Elson CO (1989) Cholera toxin and its subunits as potential oral adjuvants. Immunol Today 146:29–33

    CAS  Google Scholar 

  • Elson CO, Ealding W (1984a) Cholera toxin feeding did not induce oral tolerance in mice and abrogated oral tolerance to an unrelated protein antigen. J Immunol 133:2892–2897

    PubMed  CAS  Google Scholar 

  • Elson CO, Ealding W (1984b) Generalized systemic and mucosal immunity in mice after mucosal stimulation with cholera toxin. J Immunol 132:2736–2741

    PubMed  CAS  Google Scholar 

  • Elson CO, Holland SP, Dertzbaugh MT, Cuff CF, Anderson AO (1995) Morphologic and functional alterations of mucosal T cells by cholera toxin and its B subunit. J Immunol 154:1032–1040

    PubMed  CAS  Google Scholar 

  • Field M (1980) Regulation of small intestinal ion transport by cyclic nucleotides and calcium. In: Field M, Fordtran JS, Schultz SG (eds) Secretory diarrhea. Waverly, Baltimore pp 21–30

    Google Scholar 

  • Fontana MR, Manetti R, Giannelli V, Magagnoli C, Marchini A, Olivieri R, Domenighini M, Rappuoli R, Pizza M (1995) Construction of nontoxic derivatives of cholera toxin and characterization of the immunological response against the A subunit. Infect Immun 63:2356–2360

    PubMed  CAS  Google Scholar 

  • Harford S, Dykes CW, Hobden AN, Read MJ, Halliday IJ (1989) Inactivation of the Escherichia coli heat-labile enterotoxin by in vitro mutagenesis of the A-subunit gene. Eur J Biochem 183:311–316

    Article  PubMed  CAS  Google Scholar 

  • Häse CC, Thai LS, Boesman-Finkelstein M, Mar VL, Burnette WN, Kaslow HR, Stevens LA, Moss J, Finkelstein RA (1994) Construction and characterization of recombinant Vibrio cholerae strains producing inactive cholera toxin analogs. Infect Immun 62:3051–3057

    PubMed  Google Scholar 

  • Hashigucci K, Ogawa H, Ishidate T, Yamashita R, Kamiya H, Watanabe K, Hattori N, Sato T, Suzuki Y, Nagamine T, Aizawa C, Tamura S, Kurata T, Oya A (1996) Antibody responses in volunteers induced by nasal influenza vaccine combined with Escherichia coli heat-labile enterotoxin B subunit containing a trace amount of the holotoxin. Vaccine 14:113–119

    Article  PubMed  CAS  Google Scholar 

  • Hathaway LJ, Partidos CD, Vohra P, Steward MW (1995) Induction of systemic immune responses to measles virus synthetic peptides administered intranasally. Vaccine 13:1495–1500

    Article  PubMed  CAS  Google Scholar 

  • Hornquist E, Lycke N (1993) Cholera toxin adjuvant greatly promotes antigen priming of T cells. Eur J Immunol 23:2136–2143

    Article  PubMed  CAS  Google Scholar 

  • Katz JM, Lu X, Galphin JC, Clements JD (1996) Heat-labile enterotoxin from Escherichia coli as an adjuvant for oral influenza vaccination. In: Brown LE, Hampson AW, Webster RG (eds) Options for the control of influenza. III. Elsevier, New York, pp 292–297

    Google Scholar 

  • Katz JM, Lu X, Young SA, Galphin JC (1997) Adjuvant activity of the heat-labile enterotoxin from enterotoxigenic Escherichia coli for oral administration of inactivated influenza virus vaccine. J Infect Dis 175:352–363

    Article  PubMed  CAS  Google Scholar 

  • Lee CK, Weltzin R, Thomas WD, Kleanthous H, Ermak TH, Soman G, Hill JE, Ackerman SK, Monath TP (1995) Oral immunization with recombinant Helicobacter pylori urease induces secretory IgA antibodies and protects mice from challenge with Helicobacter felis. J Infect Dis 172:161–171

    Article  PubMed  CAS  Google Scholar 

  • Levine MM, Kaper JB, Black RE, Clements ML (1983) New knowledge on pathogenesis of bacterial enteric infections as applied to vaccine development. Microbiol Rev 47:510–550

    PubMed  CAS  Google Scholar 

  • Lobet Y, Cluff CW, Cieplak W, Jr. (1991) Effect of site-directed mutagenic alterations on ADP-rib- osyltransferase activity of the A subunit of Escherichia coli heat-labile enterotoxin. Infect Immun 59:2870–2879

    PubMed  CAS  Google Scholar 

  • Lowell G, Kaminski R, VanCott T, Slike B, Kersey K, Zawoznik E, Loomis-Price L, Smith G, Redfield R, Amselem S, Brix D (1997) Proteosomes, emulsions, and cholera toxin B improve nasal immunogenicity of human immunodeficiency virus gp l60 in mice: induction of serum, intestinal, vaginal, and lung IgA and IgG. J Infect Dis 175:292–301

    Article  PubMed  CAS  Google Scholar 

  • Lycke N, Karlsson U, Sjolander A, Magnusson K-E (1991) The adjuvant effect of cholera toxin is associated with an increased intestinal permeability for luminal antigens. Scand J Immunol 33:691–698

    Article  PubMed  CAS  Google Scholar 

  • Lycke N, Tsuji T, Holmgren J (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

    Article  PubMed  CAS  Google Scholar 

  • Mason HS, Ball JM, Shi J-J, Jiang X, Estes MK, Arntzen CJ (1996) Expression of Norwalk virus capsid protein in transgenic tobacco and potato plants and its oral immunogenicity in mice. Proc Natl Acad Sci USA 93:5335–5340

    Article  PubMed  CAS  Google Scholar 

  • McGhee JR, Kiyono H (1993) New perspectives in vaccine development: mucosal immunity to infections. Infect Agents Dis 12:55–73

    Google Scholar 

  • Merritt EA, Sarfaty S, Pizza M, Domenighini M, Rappuoli R, Hol WG (1995) Mutation of a buried residue causes loss of activity but no conformational change in the heat-labile enterotoxin of Escherichia coli. Nat Struct Biol 2:269–272

    Article  PubMed  CAS  Google Scholar 

  • Mosmann TR, Coffman RL (1989) TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Ann Rev Immunol 7:145–173

    Article  CAS  Google Scholar 

  • Moss J, Stanley SJ, Vaughan M, Tsuji T (1993) Interaction of ADP-ribosylation factor with Escherichia coli enterotoxin that contains an inactivating lysine 112 substitution. J Biol Chem 268:6383–6387

    PubMed  CAS  Google Scholar 

  • Nedrud JG, Sigmund N (1991) Cholera toxin as a mucosal adjuvant. III. Antibody responses to non- target dietary antigens are not increased. Reg Immunol 3:217–222

    CAS  Google Scholar 

  • Oplinger ML, Baqar S, Trofa AF, Clements JD, Gibbs P, Pazzaglia G, Bourgeois AL, Scott. DA (1997) Safety and immunogenicity in volunteers of a new candidate oral mucosal adjuvant, LT(R192G). In: Program and abstracts of the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy. Am Soc Microbiol, Washington, DC

    Google Scholar 

  • Partidos CD, Pizza M, Rappuoli R, Steward MW (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

    Article  PubMed  CAS  Google Scholar 

  • Pizza M, Domenighini M, Hol W, Giannelli V, Fontana MR, Giuliani MM, Magagnoli C, Peppoloni S, Manetti R, Rappuoli R (1994) Probing the structure-activity relationship of Escherichia coli LT-A by site-directed mutagenesis. Mol Microbiol 14:51–60

    Article  PubMed  CAS  Google Scholar 

  • Quaroni A, Isselbachre K (1981) Cytotoxic effects and metabolism of benzo(a)pyrene and 7, 12-diam-ethylbenzene (a)-anthrazene in duodenal and ileal epithelial cell cultures. J Natl Cancer Inst 67:1353- 1359

    PubMed  CAS  Google Scholar 

  • Roberts M, Bacon A, Rappuoli R, Pizza M, Cropley I, Douce G, Dougan G, Marinaro M, McGhee J, Chatfield S (1995) A mutant pertussis toxin molecule that lacks ADP-ribosyltransferase activity, PT- 9K/129G, is an effective mucosal adjuvant for intranasally delivered protein. Infect Immun 63:2100- 2108

    PubMed  CAS  Google Scholar 

  • Romagnani S (1991) Human Thl and Th2 subsets: doubt no more. Immunol Today 12:256–257

    Article  PubMed  CAS  Google Scholar 

  • Sixma TK, Pronk SE, Kalk KH, Wartna ES, van Zanten BAM, Witholt B, Hol WGJ (1991) Crystal structure of a cholera toxin-related heat-labile enterotoxin from E. coli. Nature (London) 351:371–377

    Article  CAS  Google Scholar 

  • Sixma TK, Kalk KH, van Zanten BAM, Dauter Z, Kingma J, Witholt B, Hoi WGJ (1993) Refined structure of Escherichia coli heat-labile enterotoxin, a close relative of cholera toxin. J Mol Biol 230:890–918

    Article  PubMed  CAS  Google Scholar 

  • Snider DP, Marshall JS, Perdue MH, Liang H (1994) Production of IgE antibody and allergic sensitization of intestinal and peripheral tissues after oral immunization with protein Ag and cholera toxin. J Immunol 53:647–657

    Google Scholar 

  • Staats HF, Nichols WG, Palker TJ (1996) Systemic and vaginal antibody responses after intranasal immunization with HIV-1 C4/V3 peptide T1SP10 MN(A). J Immunol 157:462–472

    PubMed  CAS  Google Scholar 

  • Takahashi I, Marinaro M, Kiyono H, Jackson RJ, Nakagawa I, Fujihashi K, Hamada S, Clements JD, Bost KL, McGhee JR (1996) Mechanisms for mucosal immunogenicity and adjuvanticity of Escherichia coli labile enterotoxin. J Infect Dis 173:627–635

    Article  PubMed  CAS  Google Scholar 

  • Tribble DR, Baqar S, Oplinger ML, Bourgeois AL, Clements JD, Pazzaglia G, Pace J, Walker RI, Gibbs P, Scott DA (1997) Safety and enhanced immunogenicity in volunteers of an oral, inactivated whole cell Campylobacter vaccine co-administered with a modified E. coli heat-labile enterotoxin adjuvant - LT(R192G). In: Program and abstracts of the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy. Am Soc Microbiol, Washington, DC

    Google Scholar 

  • Tsuji T, Inoue T, Miyama A, Okamoto K, Honda T, Miwatani T (1990) A single amino acid substitution in the A subunit of Escherichia coli enterotoxin results in loss of its toxic activitiy. J Biol Chem 265:22520–22525

    PubMed  CAS  Google Scholar 

  • Tsuji T, Inoue T, Miyama A, Noda M (1991) Glutamic acid-112 of the A subunit of heat-labile enterotoxin from enterotoxigenic Escherichia coli is important for ADP-ribosyltransferase activity. FEBS Lett 291:319–321

    Article  PubMed  CAS  Google Scholar 

  • Tsuji wamoto Y, Miyama A, Asano Y (1997) Relationship between a low toxicity of the mutant A subunit of enterotoxigenic Escherichia coli enterotoxin and its strong adjuvant action. Immunology 90:176–182

    Article  PubMed  CAS  Google Scholar 

  • Urban JF, Madden KB, Svetic A, Cheever A, Trotta PP, Gause WC, Katona IM, Finkelman FD (1992) The importance of TH2 cytokines in protective immunity to nematodes. Immunol Rev 127:205–220

    Article  PubMed  CAS  Google Scholar 

  • Van de Verg L, Hartman A, Bhattacharjee A, Tall B, Yuan L, Sasala K, Hadfield T, Zollinger W, Hoover D, Warren R (1996) Outer membrane protein of Neisseria meningitidis as a mucosal adjuvant for lipopolysaccharide of Brucella melitensis in mouse and guinea pig intranasal immunization models. Infect Immun 64:5263–5268

    Google Scholar 

  • Volkheimer G, Schulz FH (1968) The phenomenon of persorption. Digestion 1:213–218

    Article  PubMed  CAS  Google Scholar 

  • Weltzin R, Kleanthous H, Guirakhoo F, Monath TP, Lee CK (1997) Novel intranasal immunization techniques for antibody induction and protection of mice against gastric Helicobacter felis infection. Vaccine 4:370–376

    Article  Google Scholar 

  • Wilson AD, Bailey M, Williams NA, Stokes CR (1991) The 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 21:2333–2339

    Article  PubMed  CAS  Google Scholar 

  • Wu Y-Y, Nahm MH, Guo Y, Russell MW, Briles DE (1997) Intranasal immunization of mice with PspA (pneumococcal surface protein A) can prevent intranasal carriage, pulmonary infection, and sepsis with Streptococcus pneumoniae. J Infect Dis 175:839–846

    Article  PubMed  CAS  Google Scholar 

  • Xu-Amano J, Kiyono H, Jackson RJ, Staats HF, Fujihashi K, Burrows PD, Elson CO, Pillai S, McGhee JR (1993) Helper T cell subsets for immunoglobulin A responses: oral immunization with tetanus toxoid and cholera toxin as adjuvant selectively induces Th2 cells in mucosal associated tissues. J Exp Med 178:1309–1320

    Article  PubMed  CAS  Google Scholar 

  • Xu-Amano J, Jackson RJ, Fujihashi K, Kiyono H, Staats HF, McGhee JR (1994) Helper Thl and Th2 cell responses following mucosal or systemic immunization with cholera toxin. Vaccine 12:903–911

    Article  PubMed  CAS  Google Scholar 

  • Yamamoto M, Vancott JL, Okahashi N, Marimanr M, Kiyono H, Fujihashi K, Jackson RJ, Chatfield SN, Bluethmann H, McGhee JR (1996) The role of Thl and Th2 cells for mucosal IgA responses. Ann NY Acad Sci 778:64–71

    Article  PubMed  CAS  Google Scholar 

  • Yamamoto S, Kiyono H, Yamamoto M, Imaoka K, Yamamoto M, Fujihashi K, VanGinkel FW, Noda M, Takeda Y, McGhee JR (1997a) A nontoxic mutant of cholera toxin elicits Th-2 type responses for enhanced mucosal immunity. Proc Natl Acad Sci USA 94:5267–5272

    Article  PubMed  CAS  Google Scholar 

  • Yamamoto S, Takeda Y, Yamamoto M, Kurazono H, Imaoka K, Yamamoto M, Fujihashi K, Noda M, Kiyono H, McGhee JR (1997b) Mutants in the ADP-ribosyltransferase cleft of cholera toxin lack diarrheagenicity but retain adjuvanticity. J Exp Med 185:1203–1210

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Tulane University Medical Center, 1430 Tulane Avenue, New Orleans, LA, 70112, USA

    L. C. Freytag & J. D. Clements

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  1. L. C. Freytag
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  2. J. D. Clements
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Editors and Affiliations

  1. Swiss Institute for Experimental Cancer Research Institute of Biochemistry, University of Lausanne, Ch. des Boveresses 155, CH-1066, Epalinges, Switzerland

    Jean-Pierre Kraehenbuhl

  2. GI Cell Biology Laboratory, Children’s Hospital and Harvard Medical School, 300 Longwood Ave., Boston, MA, 02115, USA

    Marian R. Neutra

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© 1999 Springer-Verlag Berlin Heidelberg

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Freytag, L.C., Clements, J.D. (1999). Bacterial Toxins as Mucosal Adjuvants. In: Kraehenbuhl, JP., Neutra, M.R. (eds) Defense of Mucosal Surfaces: Pathogenesis, Immunity and Vaccines. Current Topics in Microbiology and Immunology, vol 236. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59951-4_11

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  • DOI: https://doi.org/10.1007/978-3-642-59951-4_11

  • Publisher Name: Springer, Berlin, Heidelberg

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