Vibrio cholerae

Molecular Pathogenesis, Immune Response, and Vaccine Development
  • Matthew K. Waldor
  • John J. Mekalanos
Part of the Infectious Agents and Pathogenesis book series (IAPA)

Abstract

The curved, gram-negative bacterium Vibrio cholerae is the cause of cholera, a severe and potentially lethal diarrheal disease. The disease has been recognized since ancient times and descriptions of cholera can be found in Sanskrit texts dating back to 500 B.C. (1) Besides its often dramatic clinical presentation, two epidemiologic features distinguish cholera from other diarrheal diseases. These are the tendency of cholera to appear in explosive outbreaks and its predilection for pandemic spread. The explosiveness of a cholera outbreak was sadly witnessed in 1994 with the massive death counts in the refugee camps of Goma, Zaire.

Keywords

Cholera Toxin Vibrio CHOLERAE Cholera Outbreak Cholerae Strain Cholera Vaccine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Barua, D., 1992, History of cholera, in: Cholera (D. Barua and W. B. Greenough III, eds.), Plenum Press, New York, pp. 1–36.Google Scholar
  2. 2.
    Shimada, T., Nair, G. B., Deb, B. C., Albert, M.J., Sack, R. B., and Takeda, Y, 1993, Outbreak of Vibrio cholerae non-Ol in India and Bangladesh, Lancet 341:1347.CrossRefGoogle Scholar
  3. 3.
    Wachsmuth, I. K., Blake, P. A., and Olsvik, Ø. (eds.), 1994, Vibrio cholerae and Cholera: Molecular to Global Perspectives, ASM Press, Washington, D.C.Google Scholar
  4. 4.
    Barua, D., and Greenough, W. B., 1992, Cholera, Plenum Medical, New York.Google Scholar
  5. 5.
    Kaper, J. B., Morris, J. G., and Levine, M. M., 1995, Cholera, Clin. Microbiol. Rev. 8:48–86.PubMedGoogle Scholar
  6. 6.
    Shimada, T., Arakawa, E., Itoh, K., Okitsu, T., Matsushima, A., Asai, Y., Yamai, S., Nakazato, T., Nair, G. B., Albert, M. J., and Takeda, Y, 1994, Extended serotyping scheme for Vibrio cholerae, Curr. Microbiol. 28:175–178.CrossRefGoogle Scholar
  7. 7.
    Morris, J. G., 1990, Non-O group 1 Vibrio cholerae. A look at the epidemiology of an occasional pathogen, Epidemiol. Rev. 12:179–191.PubMedGoogle Scholar
  8. 8.
    Wachsmuth, I. K., Evins, G. M., Fields, P. I., Olsvik, O., Popovic, T., Bopp, C. A., Wells, J. G., Carrillo, C., and Blake, P. A., 1993, The molecular epidemiology of cholera in Latin America, J. Infect. Dis. 167:621–626.PubMedCrossRefGoogle Scholar
  9. 9.
    Manning, P. A., Stroeher, U. H., and Morona, R., 1994, Molecular basis for O-antigen biosynthesis in Vibrio cholerae O1: Ogawa-Inaba switching, in: Vibrio cholerae and Cholera: Molecular to Global Perspectives (I. K. Wachsmuth, P. A. Blake, and Ø. Olsvik, eds.), ASM Press, Washington, D.C., pp. 77–94.Google Scholar
  10. 10.
    Siddique, A. K., Baqui, A., Eusof, A., Haider, K., Hossain, M., Bashir, I., and Zaman, K., 1991, Survival of classic cholera in Bangladesh, Lancet 337:1125–1127.PubMedCrossRefGoogle Scholar
  11. 11.
    Popovic, T., Bopp, C., Olsvik, Ø., and Wachsmuth, I. K., 1993, Epidemiologic application of a standardized ribotype scheme for Vibrio cholerae Ol, J. Clin. Microbiol. 31:2474–2482.PubMedGoogle Scholar
  12. 12.
    Taylor, R., Shaw, C., Peterson, K., Spears, P., and Mekalanos, J., 1988, Safe, live Vibrio cholerae vaccines? Vaccine 6:151–154.PubMedCrossRefGoogle Scholar
  13. 13.
    Waldor, M. K., and Mekalanos, J. J., 1994, ToxR regulates virulence gene expression in non-Ol strains of Vibrio cholerae that cause epidemic cholera, Infect. Immun. 62:72–78.PubMedGoogle Scholar
  14. 14.
    Calia, K. E., Murtagh, M., Ferraro, M. J., and Calderwood, S. B., 1994, Comparison of Vibrio cholerae O139 with V. cholerae Ol classical and El Tor biotypes, Infect. Immun. 62:1504–1506.PubMedGoogle Scholar
  15. 15.
    Cholera Working Group, 1993, Large epidemic of cholera-like disease in Bangladesh caused by Vibrio cholerae O139 synonym Bengal, Lancet 342:387–390.CrossRefGoogle Scholar
  16. 16.
    Hall, R. H., Khambaty, F. M., Kothary, M., and Keasler, S. D., 1993, Non-Ol Vibrio cholerae, Lancet 342:430.PubMedCrossRefGoogle Scholar
  17. 17.
    Waldor, M. K., and Mekalanos, J.J., 1994, Vibrio choleraeO139 specific gene sequences, Lancet 343:1366.PubMedCrossRefGoogle Scholar
  18. 18.
    Waldor, M. K., Colwell, R., and Mekalanos, J. J., 1994, The Vibrio cholerae O139 serogroup antigen includes O-antigen capsule and lipopolysaccharide virulence determinants, Proc. Natl. Acad. Sci. USA 91:11388–11392.PubMedCrossRefGoogle Scholar
  19. 19.
    Bik, E. M., Bunschoten, A. E., Gouw, R. D., and Mooi, E, 1995, Genesis of the novel epidemic Vibrio cholerae O139 strain: Evidence for horizontal transfer of genes involved in polysac-charide synthesis, EMBO J. 14:209–216.PubMedGoogle Scholar
  20. 20.
    Mintz, E. D., Popovic, T., and Blake, P. A., 1994, Transmission of Vibrio choleraeOl, in: Vibrio cholerae and Cholera: Molecular to Global Perspectives (I. K. Wachsmuth, P. A. Blake, and Ø. Olsvik, eds.), ASM Press, Washington, D. C., pp. 345–356.Google Scholar
  21. 21.
    Levine, M. M., Kaper, J. B., Black, R. E., and Clements, M. L., 1983, New knowledge on pathogenesis of bacterial enteric infections as applied to vaccine development, Microbiol. Rev. 47:510–550.PubMedGoogle Scholar
  22. 22.
    Finkelstein, R. A., 1992, Cholera enterotoxin (choleragen): A historical perspective, in: Cholera (D. Barua and W. B. Greenough III, eds.), Plenum Press, New York, pp. 155–187.Google Scholar
  23. 23.
    Gabriel, S. E., Brigman, K. N., Koller, B. H., Boucher, R. C., and Stutts, M. J., 1994, Cystic fibrosis heterozygote resistance to cholera toxin in the cystic fibrosis mouse model, Science 266:107–109.PubMedCrossRefGoogle Scholar
  24. 24.
    Peterson, J. W., and Ochoa, G. L., 1989, Role of prostaglandins and cAMP in the secretory effects of cholera toxin, Science 245:857–859.PubMedCrossRefGoogle Scholar
  25. 25.
    Cassuto, J., Jodal, M., Tuttle, R., and Lundgren, O., 1981, On the role of intramural nerves in cholera toxin induced intestinal secretion, Scand. J. Gastroenterol. 16:377–384.PubMedCrossRefGoogle Scholar
  26. 26.
    Pearson, G. D., and Mekalanos, J. J., 1982, Molecular cloning of Vibrio cholerae enterotoxin genes in Escherichia coli K-12, Proc. Natl. Acad. Sci. USA 79:2976–2980.PubMedCrossRefGoogle Scholar
  27. 27.
    Mekalanos, J. J., Swartz, D. J., Pearson, G. D., Harford, N., Groyne, E, and deWilde, M., 1983, Cholera toxin genes: Nucleotide sequence, deletion analysis and vaccine development, Nature 306:551–557.PubMedCrossRefGoogle Scholar
  28. 28.
    Kaper, J. B., Lockman, H., Balini, M., and Levine, M. M., 1984, Recombinant nontox-inogenic Vibrio cholerae strains as attenuated cholera vaccine candidates, Nature 308: 655–658.PubMedCrossRefGoogle Scholar
  29. 29.
    Pearson, G. D. N., Woods, A., Chiang, S. L., and Mekalanos, J.J., 1993, CTX genetic element encodes a site-specific recombination system and an intestinal colonization factor, Proc. Natl. Acad. Sci. USA 90:3750–3754.PubMedCrossRefGoogle Scholar
  30. 30.
    Fasano, A., Baudry, B., Pumplin, D. W., Wasserman, S. S., Tall, B. D., Ketley, J. N., and Kaper, J. B., 1991, Vibrio cholerae produces a second enterotoxin which affects intestinal tight junctions, Proc. Natl. Acad. Sci. USA 88:5242–5246.PubMedCrossRefGoogle Scholar
  31. 31.
    Trucksis, M., Galen, J., Michalski, J., Fasano, A., and Kaper, J. B., 1993, Accessory cholera enterotoxin (Ace), the third toxin of a Vibrio cholerae virulence cassette, Proc. Natl. Acad. Sci. USA 90:5267–5271.PubMedCrossRefGoogle Scholar
  32. 32.
    Levine, M. M., Kaper, J. B., Herrington, D., Losonsky, G., Morris J. G., Clements, M., Black, R. E., Tall, B., and Hall, R., 1988, Volunteer studies of deletion mutants of Vibrio cholerae Ol prepared by recombinant techniques, Infect. Immun. 56:161–167.PubMedGoogle Scholar
  33. 33.
    Mekalanos, J. J., and Sadoff, J. C., 1994, Cholera vaccines: Fighting an ancient scourge, Science 265:1387–1389.PubMedCrossRefGoogle Scholar
  34. 34.
    Koonin, E. V., 1992, The second cholera toxin, Zot, and its plasmid-encoded and phage-encoded homologues constitute a group of putative ATP-ases with an altered purine NTP-binding motif, FEBS Lett. 312:3–6.PubMedCrossRefGoogle Scholar
  35. 35.
    Taylor, D. N., Killeen, K. P., Hack, D. C., Kenner, J. R., Coster, T. S., Beattie, D. T., Ezzell, J., Hyman, T., Troga, A., Sjogren, M. H., Friedlander, A., Mekalanos, J. J., and Sadoff, J. C., 1994, Development of a live, oral, attenuated vaccine against El Tor cholera, J. Infect. Dis. 170:1518–1523.PubMedCrossRefGoogle Scholar
  36. 36.
    Tacket, C. O., Losonsky, G., Nataro, J. P., Cryz, S. J., Edelman, R., Fasano, A., Michalski, J., Kaper, J. B., and Levine, M. M., 1993, Safety and immunogenicity of live oral cholera vaccine candidate CVD 110, a ΔctxA Δzot Δ ace derivative of El Tor Ogawa Vibrio cholerae, J. Infect. Dis. 168:1536–1540.PubMedCrossRefGoogle Scholar
  37. 37.
    Honda, T., and Finkelstein, R. A., 1979, Purification and characterization of a hemolysin produced by Vibrio cholerae biotype El Tor: Another toxic substance produced by cholera vibrios, Infect. Immun. 26:1020–1027.PubMedGoogle Scholar
  38. 38.
    Ichinose, Y., Yamamoto, K., Nakasone, N., Tanabe, M. J., Takeda, T., Miwatani, T., and Iwanaga, M., 1987, Enterotoxicity of El Tor-like hemolysin of non-Ol Vibrio cholerae, Infect. Immun. 55:1090–1093.PubMedGoogle Scholar
  39. 39.
    O’Brien, A. D., Chen, M. E., Holmes, R. K., Kaper, J., and Levine, M. M., 1984, Environmental and human isolates of Vibrio cholerae and Vibrio parahaemolyticus produce a Shigella dysenteriae 1 (Shiga)-like cytotoxin, Lancet 1:77–78.PubMedCrossRefGoogle Scholar
  40. 40.
    Saha, S., and Sanyal, S. C., 1988, Cholera toxin gene-positive Vibrio cholerae Ol Ogawa and Inaba strains produce the new cholera toxin, FEMS Microbiol. Lett. 50:113–116.CrossRefGoogle Scholar
  41. 41.
    Pierce, N. F., Kaper, J. B., Mekalanos, J. J., and Cray, W. J., 1985, Role of cholera toxin in enteric colonization by Vibrio cholerae Ol in rabbits, Infect. Immun. 50:813–816.PubMedGoogle Scholar
  42. 42.
    Freter, R., O’Brien, P. C. M., and Macsai, M. M. S., 1981, Role of chemotaxis in the association of motile bacteria with intestinal mucosa in vivo studies, Infect. Immun. 34: 234–240.PubMedGoogle Scholar
  43. 43.
    Taylor, R. K., Miller, V. L., Furlong, D. B., and Mekalanos, J. J., 1987, Use of phoA gene fusions to identify a pilus colonization factor coordinately regulated with cholera toxin, Proc. Natl. Acad. Sci. USA 84:2833–2837.PubMedCrossRefGoogle Scholar
  44. 44.
    Kaufman, M. R., and Taylor, R. K., 1994, The toxin-coregulated pilus: Biogenesis and function, in: Vibrio cholerae and Cholera: Molecular to Global Perspectives (I. K. Wachsmuth, P. A. Blake, and Ø. Olsvik, eds.), ASM Press, Washington, D.C., pp. 187–202.Google Scholar
  45. 45.
    Ogierman, M. A., Zabihi, S., Mourtzios, L., and Manning, P. A., 1993, Genetic organization and sequence of the promoter-distal region of the tcp gene cluster of Vibrio cholerae, Gene 126: 51–60.PubMedCrossRefGoogle Scholar
  46. 46.
    Kaufman, M. R., Shaw, C. E., Jones, I. D., and Taylor, R. K., 1993, Biogenesis and regulation of the Vibrio cholerae toxin-coregulated pilus: Analogies to other virulence factor secretory systems, Gene 126:43–49.PubMedCrossRefGoogle Scholar
  47. 47.
    Peek, J. A., and Taylor, R. K., 1992, Characterization of a periplasmic thiol:disulfide interchange protein required for the functional maturation of secreted virulence factors of Vibrio cholerae, Proc. Natl. Acad. Sci. USA 89:6210–6214.PubMedCrossRefGoogle Scholar
  48. 48.
    Herrington, D. A., Hall, R. H., Losonsky, G., Mekalanos, J. J., Taylor, R. K., and Levine, M. M., 1988, Toxin, toxin-coregulated pili, and the toxR regulon are essential for Vibrio cholerae pathogenesis in humans, J. Exp. Med. 168:1487–1492.PubMedCrossRefGoogle Scholar
  49. 49.
    Rhine, J. A., and Taylor, R. K., 1994, TcpA pilin sequences and colonization requirements for Ol and O139 Vibrio cholerae, Mol. Microbiol. 13:1013–1020.PubMedCrossRefGoogle Scholar
  50. 50.
    Attridge, S. R., Voss, E., and Manning, P. A., 1993, The role of toxin-coregulated pili in the pathogenesis of Vibrio cholerae Ol El Tor, Microb. Pathog. 15:421–431.PubMedCrossRefGoogle Scholar
  51. 51.
    Parsot, C., Taxman, E., and Mekalanos, J. J., 1991, ToxR regulates the production of lipoproteins and the expression of serum resistance in Vibrio cholerae, Proc. Natl. Acad. Sci. USA 88:1641–1645.PubMedCrossRefGoogle Scholar
  52. 52.
    Everiss, K. D., Hughes, K.J., Kovach, M. E., and Peterson, K. M., 1994, The Vibrio cholerae acfB colonization determinant encodes an inner membrane protein that is related to a family of signal-transducing proteins, Infect. Immun. 62:3289–3298.PubMedGoogle Scholar
  53. 53.
    Peterson, K. M., and Mekalanos, J. J., 1988, Characterization of the Vibrio cholerae ToxR regulon: Identification of novel genes involved in intestinal colonization, Infect. Immun. 56:2822–2829.PubMedGoogle Scholar
  54. 54.
    Gardel, C. L., and Mekalanos, J. J., 1994, Modus operandi of Vibrio cholerae. Swim to arrive, stop to kill. The relationship among chemotaxis, motility and virulence, J. Cell Biochem. 18A:65.Google Scholar
  55. 55.
    Franzon, V. L., Barker, A., and Manning, P. A., 1993, Nucleotide sequence encoding the mannose-fucose resistant hemagglutinin of Vibrio cholerae Ol and construction of a mutant, Infect. Immun. 61:3032–3037.PubMedGoogle Scholar
  56. 56.
    Jonson, G., Lebens, M., and Holmgren, J., 1994, Cloning and sequencing of Vibrio cholerae mannose-sensitive haemagglutinin pilin gene: Localization of mshA within a cluster of type 4 pilin genes, Mol. Microbiol. 13:109–118.PubMedCrossRefGoogle Scholar
  57. 57.
    Finkelstein, R. A., Boesman-Finkelstein, M., Chang, Y, and Hase, C. C., 1992, Vibrio cholerae hemagglutinin/protease, colonial variation, virulence, and detachment, Infect. Immun. 60: 472–478.PubMedGoogle Scholar
  58. 58.
    Henderson, D. P., and Payne, S. M., 1994, Vibrio cholerae iron transport systems: Roles of heme and siderophore iron transport in virulence and identification of a gene associated with multiple iron transport systems, Infect. Immun. 62:5120–5125.PubMedGoogle Scholar
  59. 59.
    Goldberg, M. B., DiRita, V. J., and Calderwood, S. B., 1990, Identification of an iron-regulated virulence determinant in Vibrio cholerae, using TnphoA mutagenesis, Infect. Immun. 58:55–60.PubMedGoogle Scholar
  60. 60.
    Camilli, A., Beattie, D., and Mekalanos, J., 1994, Use of genetic recombination as a reporter of gene expression, Proc. Natl. Acad. Sci. USA 91:2634–2638.PubMedCrossRefGoogle Scholar
  61. 61.
    Overbye, L. J., Sandkvist, M., and Bagdasarian, M., 1993, Genes required for extracellular secretion of enterotoxin are clustered in Vibrio cholerae, Gene 132:101–106.PubMedCrossRefGoogle Scholar
  62. 62.
    Hall, R. H., Vial, P. A., Kaper, J. B., Mekalanos, J. J., and Levine, M. M., 1988, Morphological studies on fimbriae expressed by Vibrio cholerae Ol, Microb. Pathog. 4:257–65.PubMedCrossRefGoogle Scholar
  63. 63.
    Baselski, V. S., Medina, R. A., and Parker, C. D., 1979, In vivo and in vitro characterization of virulence deficient mutants of Vibrio cholerae, Infect. Immun. 24:111–116.PubMedGoogle Scholar
  64. 64.
    Ottemann, K. M., and Mekalanos, J. J., 1994, Regulation of cholera toxin expression, in: Vibrio cholerae and Cholera: Molecular to Global Perspectives (I. K. Wachsmuth, P. A. Blake, and Ø. Olsvik, eds.), ASM Press, Washington, D.C., pp. 177–185.Google Scholar
  65. 65.
    DiRita, V.J., 1992, Co-ordinate expression of virulence genes by ToxR in Vibrio cholerae, Mol. Microbiol. 6:451–458.PubMedCrossRefGoogle Scholar
  66. 66.
    Lang, H., Jonson, G., Holmgren, J., and Palva, E. T., 1994, The maltose regulon of Vibrio cholerae affects production and secretion of virulence factors, Infect. Immun. 62:4781–4788.PubMedGoogle Scholar
  67. 67.
    Litwin, C. M., and Calderwood, S. B., 1994, Analysis of the complexity of gene regulation by Fur in Vibrio cholerae, J. Bacteriol. 176:240–248.PubMedGoogle Scholar
  68. 68.
    Williams, S. G., Attridge, S. R., and Manning, P. A., 1993, The transcriptional activator HlyU of Vibrio cholerae. Nucleotide sequence and role in virulence gene expression, Mol. Microbiol. 9:751–760.PubMedCrossRefGoogle Scholar
  69. 69.
    Richardson, S. H., 1994, Host susceptibility, in: Vibrio cholerae and Cholera: Molecular to Global Perspectives (I. K. Wachsmuth, P. A. Blake, and Ø. Olsvik, eds.), ASM Press, Washington, D.C., pp. 273–292.Google Scholar
  70. 70.
    Levine, M. M., and Pierce, N. F., 1992, Immunity and vaccine development, in: Cholera (D. Barua and W. B. Greenough III, eds.), Plenum Press, New York, pp. 285–328.Google Scholar
  71. 71.
    Clemens, J. D., Sack, D. A., Harris, J. R., Chakraborty, J., Khan, M., Huda, S., Ahmed, F., Goes, J., Rao, M., Svennerholm, A., and Holmgren, J., 1989, ABO blood groups and cholera: New observations on specificity of risk and modification of vaccine efficacy, J. Infect. Dis. 159:770–773.PubMedCrossRefGoogle Scholar
  72. 72.
    Glass, R. I., Svennerholm, A. M., Khan, M. R., Huda, S., Huq, M. I., and Holmgren, J., 1985, Seroepidemiological studies of El Tor cholera in Bangladesh: Association of serum antibody levels with protection, J. Infect. Dis. 151:236–242.PubMedCrossRefGoogle Scholar
  73. 73.
    Clemens, J. D., Van Loon, R., Sack, D., Rao, M., Ahmed, F., Chakraborty J., Kay, B., Khan, M., Yunus, M., Harris, J., Svennerholm, A., and Holmgren, J., 1991, Biotype as determinant of natural immunising effect of cholera, Lancet 337:883–884.PubMedCrossRefGoogle Scholar
  74. 74.
    Svennerholm, A.-M., Jonson, G., and Holmgren, J., 1994, Immunity to Vibrio cholerae infection, in: Vibrio cholerae and Cholera: Molecular to Global Perspectives (I. K. Wachsmuth, P. A. Blake, and Ø. Olsvik, eds.), ASM Press, Washington, D.C., pp. 257–272.Google Scholar
  75. 75.
    Hall, R. H., Losonsky, G., Silveira, A. P., Taylor, R. K., Mekalanos, J. J., Witham, N. D., and Levine, M. M., 1991, Immunogenicity of Vibrio cholerae Ol toxin-coregulated pili in experimental and clinical cholera, Infect. Immun. 59:2508–2512.PubMedGoogle Scholar
  76. 76.
    Sun, D. X., Mekalanos, J. J., and Taylor, R. K., 1990, Antibodies directed against the toxin-coregulated pilus isolated from Vibrio cholerae provide protection in the infant mouse experimental cholera model, J. Infect. Dis. 161:1231–1236.PubMedCrossRefGoogle Scholar
  77. 77.
    Cash, R. A., Music, S. I., Libonati, J. P., Criag, J. P., Pierce, N. F., and Hornick, R. B., 1974, Reponse of man to infection with Vibrio cholerae. II. Protection from illness afforded by previous disease and vaccine, J. Infect. Dis. 130:325–333.PubMedCrossRefGoogle Scholar
  78. 78.
    Winner, L. D., Mack, J., Weltzin, R., Mekalanos, J. J., Kraehenbuhl, J. P., and Neutra, M. R., 1991, New model for analysis of mucosal immunity: Intestinal secretion of specific monoclonal immunoglobulin A from hybridoma tumors protects against Vibrio cholerae infection, Infect. Immun. 59:977–982.PubMedGoogle Scholar
  79. 79.
    Holmgren, J., Lycke, N., and Czerkinsky, C., 1993, Cholera toxin and cholera B subunit as oral-mucosal adjuvant and antigen vector systems, Vaccine 11:1179–1184.PubMedCrossRefGoogle Scholar
  80. 80.
    Lycke, N., Tsuji, T., and 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.PubMedCrossRefGoogle Scholar
  81. 81.
    McKenzie, S., and Halsey, J., 1984, Cholera toxin B subunit as a carrier protein to stimulate a mucosal immune response, J. Immunol. 133:1818–1822.PubMedGoogle Scholar
  82. 82.
    Kraehenbuhl, J. P., and Neutra, M. R., 1992, Molecular and cellular basis of immune protection of mucosal surfaces, Physiol. Rev. 72:853–879.PubMedGoogle Scholar
  83. 83.
    Sun, J.-B., Holmgren, J., and Czerkinsky, C., 1994, Cholera toxin B subunit: An efficient transmucosal carrier-delivery system for induction of peripheral immunological tolerance, Proc. Natl. Acad. Sci. USA 91:10795–10799.PubMedCrossRefGoogle Scholar
  84. 84.
    Xu-Amano, J., Kiyono, H., Jackson, R., Staats, H., Fujihashi, K., Burrows, P., Elson, C. O., Pillai, S. and McGhee, J. R., 1993, Helper T cell subsets for immunoglobulin A responses: Oral immunization with tetanus toxoid and cholera toxin as adjuvant selectively induces Th2 cells in mucosa associated tissues, J. Exp. Med. 178:1309–1320.PubMedCrossRefGoogle Scholar
  85. 85.
    Clemens, J. D., Harris, J. R., Sack, D. A., Chakraborty J., Ahmed, F., Stanton, B. F., Khan, M. U., Kay, B. A., Huda, N., and Khan, M. R., 1988, Field trial of oral cholera vaccines in Bangladesh: Results of one year of follow-up, J. Infect. Dis. 158:60–69.PubMedCrossRefGoogle Scholar
  86. 86.
    Clemens, J. D., Sack, D. A., Harris, J. R., Loon, F. V., Chakraborty J., Ahmed, F., Rao, M. R., Khan, M. R., Yunus, M. and Huda, N., 1990, Field trial of oral cholera vaccines in Bangladesh: Results from three-year follow-up, Lancet 335:270–273.PubMedCrossRefGoogle Scholar
  87. 87.
    Owen, R. L., Pierce, M. R., Apple, R. T., and Cray, W. C., 1986, M cell transport of Vibrio cholerae from the intestinal lumen into Peyer’s patches: A mechanism for antigen sampling and for microbial transepithelial migration, J. Infect. Dis. 153:1108–1118.PubMedCrossRefGoogle Scholar
  88. 88.
    Waldor, M. K., and Mekalanos, J. J., 1994, Emergence of a new cholera pandemic: Molecular analysis of virulence determinants in Vibrio cholerae O139 and development of a live vaccine prototype, J. Infect. Dis. 170:278–283.PubMedCrossRefGoogle Scholar
  89. 89.
    Clemens, J. D., Sack, D. A., Harris, J. R., Chakraborty, J., Neogy, P. K., Stanton, B., Huda, N., Khan, M. U., Kay, B. A., and Khan, M. R., 1988, Cross-protection by B subunit-whole cell cholera vaccine against diarrhea associated with heat-labile toxin-producing enterotoxi-genic Escherichia coli. Results of a large-scale field trial, J. Infect. Dis. 158:372–377.PubMedCrossRefGoogle Scholar
  90. 90.
    Coster, T. S., Killeen, K. P., Waldor, M. K., Beattie, D., Spriggs, D., Kenner, J. R., Trofa, A., Sadoff, J., Mekalanos, J. J., and Taylor, D. N., 1995, Safety, immunogenicity and efficacy of a live attenuated Vibrio cholerae O139 vaccine protype, Bengal-15, Lancet 345:949–952.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Matthew K. Waldor
    • 1
  • John J. Mekalanos
    • 1
  1. 1.Department of Microbiology and Molecular GeneticsHarvard Medical SchoolBostonUSA

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