Source: http://www.asmscience.org/content/book/10.1128/9781555818364.chap26
Timestamp: 2019-04-25 13:58:36+00:00

Document:
This chapter reviews developments and progress in the use of recombinant bacteria as live oral cholera vaccines. The extent to which a prior clinical infection with wild-type enterotoxigenic Vibrio cholerae O1 stimulates protection against cholera in the face of subsequent challenge with wildtype V. cholerae O1 comes from two sources, volunteer studies and epidemiologic studies in endemic areas. The molecular pathogenesis of cholera infection is one of the best-studied bacterial infections and is characterized by cascades of coordinately regulated virulence properties. Vibriocidal antibody is measured by bacterial lysis when serial dilutions of serum are incubated with a large standardized inoculum of V. cholerae O1 in the presence of guinea pig complement. A series of early vaccine candidates was constructed from wild-type V. cholerae strains known to be pathogenic for volunteers by introducing deletions in the chromosomal genes encoding the A (ADP-ribosylating "toxic") subunit or both the A and B (nontoxic binding) subunits of cholera enterotoxin. Investigators at the Center for Vaccine Development of the University of Maryland have identified two new toxins in addition to cholera toxin that are elaborated by virulent V. cholerae O1. The genes that encode these two toxins, zonula occludens toxin (Zot) and accessory cholera toxin (Ace), are located on the "cholera toxin element" of the cholera chromosome contiguous to ctxAB, which encodes cholera toxin. Clinical trials with candidate live oral vaccines against V. cholerae O139 are expected to commence in 1994.
Practical formulation of live oral cholera vaccine CVD 103-HgR consisting of two sachets. One sachet contains lyophilized vaccine, and the other holds a buffer powder. The contents of the buffer powder sachet and then those of the lyophilized vaccine sachet are put into a cup containing approximately 100 ml of water and stirred (either chlorinated or nonchlorinated water may be used; the ascorbic acid in the buffer powder inactivates the antibacterial effect of residual chlorine). The resultant suspension, consisting of vaccine bacteria in buffer (the “oral vaccine cocktail”), is then ingested by the subject to be vaccinated.
Two young children in Area Norte, Santiago, Chile, ingesting a “vaccine cocktail” containing a dose of CVD 103-HgR live oral cholera vaccine.
1. Baudry, B.,, A. Fasano,, J. Ketley,, and J. B. Kaper. 1992. Cloning of a gene (zot) encoding a new toxin produced by Vibrio cholerae. Infect. Immun. 60: 428– 434.
2. Benenson, A. S.,, A. Saad,, and W. H. Mosley. 1968. Serological studies in cholera. 2. The vibriocidal antibody response of cholera patients determined by a microtechnique. Bull W.H.O. 38: 277– 285.
3. Black, R. E.,, M. M. Levine,, M. L. Clements,, C. R. Young,, A.-M. Svennerholm,, and J. Holmgren. 1987. Protective efficacy in humans of killed whole-vibrio oral cholera vaccine with and without the B subunit of cholera Toxin. Infect. Immun. 55: 1116– 1120.
4. Chongsa-Nguan, M.,, W. Chaicumpa,, T. Kalambaheti,, H. Soejedi,, P. Luxananil,, S. Swasdikosa,, P. Thanasiri,, and S. Mayurasakorn. 1986. Vibriocidal antibody and antibodies to Vibrio cholerae lipopolysaccharide, cell-bound haemagglutinin and toxin in Thai population. Southeast Asian J. Trop. Med. Public Health 17: L558– 566.
5. Clemens, J. D.,, D. A. Sack,, J. Harris,, J. Chakraborty,, M. Khan,, S. Huda,, F. Ahmed,, J. Gomes,, M. Rao,, A.-M. Svennerholm,, and J. Holmgren. 1989. ABO blood groups and cholera: new observations on specificity of risk and modifications of vaccine efficacy. J. Infect. Dis. 159: 770– 773.
6. Clemens, J. D.,, D. A. Sack,, J. R. Harris,, J. Chakraborty,, M. R. Khan,, B. F. Stanton,, B. A. Kay,, M. U. Khan,, M. Yunus,, and W. Atkinson. 1986. Field trial of oral cholera vaccines in Bangladesh. Lancet ii: 124– 127.
7. Clemens, J. D.,, D. A. Sack,, J. Harris,, F. Van Loon,, J. Chakraborty,, F. Ahmed,, M. R. Rao,, M. R. Khan,, M. Yunus,, and N. Huda. 1990. Field trial of oral cholera vaccines in Bangladesh: results from three year follow-up. Lancet 335: 270– 273.
8. Clemens, J. D.,, F. Van Loon,, D. A. Sack,, J. Chakraborty,, M. R. Rao,, F. Ahmed,, J. R. Harris,, M. R. Khan,, M. Yunus,, and S. Huda. 1991. Field trial of oral cholera vaccines in Bangladesh: serum vibriocidal and antitoxic antibodies as markers of the risk of cholera. J. Infect. Dis. 163: 1235– 1242.
9. Clemens, J. D.,, F. Van Loon,, D. A. Sack,, M. R. Rao,, F. Ahmed,, J. Chakraborty,, B. A. Kay,, M. R. Khan,, M. Yunus,, J. R. Harris,, A.-M. Svennerholm,, and J. Holmgren. 1991. Biotypes as determinant of natural immunising effect of cholera. Lancet 337: 883– 884.
10. Cryz, S. J., Jr.,, M. M. Levine,, J. B. Kaper,, E. Furer,, and B. Althaus. 1990. Randomized double-blind placebo-controlled trial to evaluate the safety and immunogenicity of the live oral cholera vaccine strain CVD 103-HgR in Swiss adults. Vaccine 8: 577– 580.
11. Cryz, S. J., Jr.,, M. M. Levine,, G. Losonsky,, J. B. Kaper,, and B. Althaus. 1992. Safety and immunogenicity of a booster dose of Vibrio cholerae CVD 103-HgR live oral cholera vaccine in Swiss adults. Infect. Immun. 60: 3916– 3917.
12. Curlin, G.,, R. Levine,, K. M. S. Aziz,, A. S. M. Mizanur Rahman,, and W. F. Verwey. 1975. Field trial of cholera toxoid, 314-329. In Proceedings of the 11th Joint Conference on Cholera. National Institutes of Health, Bethesda, Md.
13. DiRita, V. J.,, C. Parsot,, G. Jander,, and J. J. Mekalanos. 1991. Regulatory cascade controls virulence in Vibrio cholerae. Proc. Natl. Acad. Sci. USA 88: 5403– 5407.
14. Fasano, A.,, B. Baudry,, D. W. Pumplin,, S. S. Wasserman,, B. D. Tall,, J. M. Ketley,, and J. B. Kaper. 1991. Vibrio cholerae produces a second enterotoxin, which affects intestinal tight junctions. Proc. Natl. Acad. Sci. USA 88: 5242– 5246.
15. Forrest, B. D.,, J. LaBrooy,, S. R. Attridge,, G. Boehm,, L. Beyer,, R. Morona,, D. J. Shearman,, and D. Rowley. 1989. A candidate live oral typhoid/cholera hybrid vaccine is immunogenic in humans. J. Infect. Dis. 159: 145– 146.
16. Glass, R. I.,, S. Becker,, I. Huq,, B. J. StoU,, M. U. Khan,, M. H. Merson,, J. V. Lee,, and R. E. Black. 1982. Endemic cholera in rural Bangladesh, 1966-1980. Am. J. Epidemiol. 116: 959– 970.
17. Glass, R. I.,, A.-M. Svennerholm,, M. R. Khan,, S. Huda,, M. I. Huq,, and J. Holmgren. 1985. Seroepidemiological studies of El Tor cholera in Bangladesh: association of serum antibody levels with protection. J. Infect. Dis. 151: 236– 242.
18. Goldberg, I.,, and J. J. Mekalanos. 1986. Effect of recA mutation on cholera toxin gene amplification and deletion events. J. Bacteriol. 165: 723– 731.
19. Gotuzzo, E.,, B. Butron,, C. Seas,, M. Penny,, R. Ruiz,, G. Losonsky,, C. F. Lanata,, S. S. Wasserman,, E. Salazar,, J. B. Kaper,, S. Cryz,, and M. M. Levine. 1993. Safety, immunogenicity and excretion pattern of single-dose live oral cholera vaccine CVD 103-HgR in Peruvian adults of high and low socioeconomic level. Infect. Immun. 61: 3994– 3997.
20. Hall, R. H.,, G. Losonsky,, A. D. P. Silveira,, R. K. Taylor,, J. J. Mekalanos,, N. D. Witham,, and M. M. Levine. 1991. Immunogenicity of Vibrio cholerae O1 toxin coregulated pili in experimental and clinical cholera. Infect. Immun. 59: 2508– 2512.
21. Herrington, D. A.,, R. H. Hall,, G. A. Losonsky,, J. J. Mekalanos,, R. K. Taylor,, and M. M. Levine. 1988. To, toxin-coregulated pili, and the toxR regulon are essential for Vibrio cholerae pathogenesis in humans. J. Exp. Med. 168: 1487– 1492.
22. Jonson, G.,, J. Holmgren,, and A.-M. Svennerholm. 1991. Epitope differences in toxin-coregulated pili produced by classical and El Tor Vibrio cholerae O1. Microb. Pathog. 11: 179– 188.
23. Jonson, G.,, A.-M. Svennerholm,, and J. Holmgren. 1989. Vibrio cholerae expresses cell surface antigens during intestinal infection which are not expressed during in vitro culture. Infect. Immun. 57: 1809– 1815.
24. Kaper, J. B.,, and M. M. Levine. 1990. Recombinant attenuated Vibrio cholerae strains used as live oral vaccines. Res. Microbiol. 141: 901– 906.
25. Kaper, J. B.,, H. Lockman,, M. M. Baldini,, and M. M. Levine. 1984. Recombinant live oral cholera vaccine. Bio/Technology 2: 345– 349.
26. Kaper, J. B.,, H. Lockman,, M. M. Baldini,, and M. M. Levine. 1984. Recombinant nontoxigenic Vibrio cholerae strains as attenuated cholera vaccine candidates. Nature (London) 308: 655– 658.
27. Ketley, J.,, J. B. Kaper,, D. A. Herrington,, G. Losonsky,, and M. M. Levine. 1990. Diminished immunogenicity of a recombination-deficient derivative of Vibrio cholerae vaccine strain CVD 103. Infect. Immun. 58: 1481– 1484.
28. Ketley, J. M.,, J. Michalski,, J. Galen,, M. M. Levine,, and J. B. Kaper. 1993. Construction of genetically-marked Vibrio cholerae Ol vaccine strains. FEMSMicrobiol. Lett., 111: 15– 21.
29. Kotloff, K.,, S. S. Wasserman,, S. A. O'Donnell,, G. A. Losonsky,, S. J. Cryz,, and M. M. Levine. 1992. Safety and immunogenicity in North Americans of a single dose of live oral cholera vaccine CVD 103-HgR: results of a randomized, placebo-controlled, double-blind crossover trial. Infect. Immun. 60: 4430– 4432.
30. Lagos, R.,, A. Avendano,, I. Horwitz,, V. Prado,, C. Ferreccio,, G. Losonsky,, S. S. Wasserman,, S. Cryz,, J. B. Kaper,, and M. M. Levine. 1993. Tolerancia e immunogenicidad de ina dosis oral de la cepa de Vibrio cholerae Ol, viva-atenuada, CVD 103-HgR: estudio de doble ciego en adultos Chilenos. Rev. Med. Chile 121: 857– 863.
31. Levine, M. M.,, R. E. Black,, M. L. Clements,, L. Cisnero,, D. R. Nalin,, and C. R. Young. 1981. The quality and duration of infection-derived immunity to cholera. J. Infect. Dis. 143: 818– 820.
32. Levine, M. M.,, R. E. Black,, M. L. Clements,, and J. B. Kaper. 1984. Present status of cholera vaccines. Biochem. Soc. Trans. 12: 200– 202.
33. Levine, M. M.,, R. E. Black,, M. L. Clements,, D. R. Nalin,, L. Cisnero,, and R. Finkelstein,. 1981. Volunteer studies in development of vaccines against cholera and enterotoxigenic Escherichia coli: a review, p. 443– 459. In T. Holme, and J. Holmgren (ed.), Acute Enteric Infections in Children: New Prospects for Treatment and Prevention. Elsevier, Amsterdam.
34. Levine, M. M.,, and J. B. Kaper. 1993. Live vaccines against cholera: an up-date. Vaccine 11: 207– 212.
35. 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.
36. Levine, M. M.,, J. B. Kaper,, D. Herrington,, J. Ketley,, G. A. Losonsky,, C. O. Tacket,, B. D. Tall,, and S. J. Cryz. 1988. Safety, immunogenicity and efficacy of recombinant live oral cholera vaccine CVD 103 and CVD 103-HgR. Lancet ii: 467– 470.
37. Levine, M. M.,, J. B. Kaper,, D. A. Herrington,, G. A. Losonsky,, J. G. Morris,, M. L. Clements,, R. E. Black,, B. D. TaU,, and R. Hall. 1988. Volunteer studies of deletion mutants of Vibrio cholerae Ol prepared by recombinant techniques. Infect. Immun. 56: 161– 167.
38. Levine, M. M.,, D. Nalin,, J. P. Craig,, D. Hoover,, E. J. Bergquist,, D. Waterman,, H. P. Holley,, R. B. Hornick,, N. F. Pierce,, and J. P. Libonati. 1979. Immunity to cholera in man: relative role of antibacterial versus antitoxic immunity. Trans. R. Soc. Trop. Med. Hyg. 73: 3– 9.
39. Levine, M. M.,, and N. F. Pierce,. 1992. Immunity and vaccine development, p. 285– 327. In W. B. Greenough III, and D. Barua (ed.), Cholera. Plenum Press, New York.
40. Losonsky, G. A.,, C. O. Tacket,, S. S. Wasserman,, J. B. Kaper,, and M. M. Levine. 1993. Secondary Vibrio cholerae specific cellular antibody responses following wild-type homologous challenge in people vaccinated with CVD 103-HgR live oral cholera vaccine: changes with time and lack of correlation and protection. Infect. Immun. 61: 729– 733.
41. Madden, J. M.,, B. A. McCardell,, and D. B. Shah. 1984. Cytotoxin production by members of genus Vibrio. Lancet i: 1217– 1218.
42. McGhee, J. R.,, J. Mestecky,, M. T. Dertzbaugh,, J. H. Eldridge,, M. Hirasawa,, and H. Kiyono. 1992. The mucosal immune system: from fundamental concepts to vaccine development. Vaccine 10: 75– 88.
43. Mekalanos, J. J.,, S. J. Swartz,, G. D. N. Pearson,, N. Harford,, F. Groyne,, and M. de Wilde. 1983. Cholera toxin genes: nucleotide sequence, deletion analysis and vaccine development. Nature (London) 306: 551– 557.
44. Michalski, J.,, J. Galen,, A. Fasano,, and J. B. Kaper. 1993. An attenuated Vibrio cholerae O1 El Tor live oral vaccine strain. Infect. Immun. 61: 4462– 4468.
45. Migasena, S.,, P. Pitisuttitham,, B. Prayurahong,, P. Suntharasami,, W. Supanaranond,, V. De-sakorn,, U. Vongsthongsri,, B. Tall,, J. Ketley,, G. Losonsky,, S. Cryz,, J. B. Kaper,, and M. M. Levine. 1989. Preliminary assessment of the safety and immunogenicity of live oral cholera vaccine strain CVD 103-HgR in healthy Thai adults. Infect. Immun. 57: 3261– 3264.
46. Miller, J. M.,, J. J. Mekalanos,, and S. Falkow. 1989. Coordinate regulation and sensory transduction in the control of bacterial virulence. Science 243: 916– 922.
47. Mosley, W. H.,, S. Ahmad,, A. S. Benenson,, and A. Ahmed. 1968. The relationship of vibriocidal antibody titre to susceptibility to cholera in family contacts of cholera patients. Bull. W.H.O. 38: 777– 785.
48. Mosley, W. H.,, A. S. Benenson,, and R. Barui. 1968. A serological survey for cholera antibodies in rural east Pakistan. I. The distribution of antibody in the control population of a cholera vaccine field-trial area and the relation of antibody titer to the partem of endemic cholera. Bull. W.H.O. 38: 327– 334.
49. Neon, S. H.,, and D. Rowley. 1970. The antigens of Vibrio cholerae involved in the vibriocidal action of antibody and complement. J. Infect. Dis. 121: 505– 513.
50. Noriki, H., 1976. Evaluation of toxic field trial on the Philippines, p. 302– 310. In H. Fukumi, and Y. Zinnaka (ed.), Proceedings of the 12th Joint Conference on Cholera. U.S.-Japan Cooperative Medical Science Program. Fuji, Tokyo.
51. O'Brien, A. D.,, M. E. Chen,, R. K. Holmes,, J. B. Kaper,, and M. M. Levine. 1984. Environmental and human isolates of Vibrio cholerae and Vibrio parahaemolyticus produce a Shigella dysenteriae 1 (Shiga)-like cytotoxin. Lancet i: 77.
52. Osek, J.,, A.-M. Svennerholm,, and J. Holmgren. 1992. Protection against Vibrio cholerae El Tor infection by specific antibodies against mannose-binding hemagglutinin pili. Infect. Immun. 60: 4961– 4964.
53. Owen, R. L.,, N. F. Pierce,, R. T. Apple,, and W. D. Cray, Jr. 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.
54. Parsot, C.,, E. Taxman,, and J. J. Mekalanos. 1991. ToxR regulates the production of lipoproteins and the expression of serum resistance in Vibrio cholerae. Proc. Natl. Acad. Sci. USA 88: 1641– 1645.
55. Pearson, G. D.,, V. J. DiRita,, M. B. Goldberg,, S. A. Boyko,, S. B. Calderwood,, and J. J. Mekalanos. 1990. New attenuated derivatives of Vibrio cholerae. Res. Microbiol. 141: 893– 899.
56. Pearson, G. D. N.,, A. Woods,, Chiang,, and J. J. Mekalanos. 1993. CTX genetic element encodes a site-specific recombination system and an intestinal colonization factor. Proc. Natl. Acad. Sci USA 90: 3750– 3754.
57. Richardson, K.,, J. B. Kaper,, and M. M. Levine. 1989. Human immune response to Vibrio cholerae O1 whole cells and isolated outer membrane protein antigens. Infect. Immun. 57: 495.
58. Roberts, A.,, G. Pearson,, and J. Mekalanos. 1992. Cholera strains derived from a 1991 Peruvian isolate of Vibrio cholerae and other El Tor strains. Abstr. 28th Joint Conf. Cholera Related Diarrheal Dis. Panel, U. S. -Japan Cooperative Medical Science Program.
59. Sciortino, C. V. 1989. Protection against infection with V. cholerae by passive transfer of mononclonal antibodies to outer membrane antigens. J. Infect. Dis. 160: 248– 252.
60. Sharma, D. P.,, S. Attridge,, J. Hackett,, and D. Rowley D. 1987. Nonlipopolysaccharide protective antigens shared by classical and El Tor biotypes of Vibrio cholerae. J. Infect. Dis. 155: 716– 723.
61. Sharma, D. P.,, C. Thomas,, R. H. Hall,, M. M. Levine,, and S. R. Attridge. 1989. Significance of toxin-coregulated pili as protective antigens of Vibrio cholerae in the infant mouse model. Vaccine 7: 451– 456.
62. Sigel, S. P.,, and S. M. Payne. 1982. Effect of iron regulation on growth, siderophore production, and expression of outer membrane proteins of Vibrio cholerae. J. Bacteriol. 150: 148– 155.
63. Simanjuntak, C. H.,, P. O'Hanley,, N. H. Punjabi,, F. Noriega,, G. Pazzaglia,, P. Dykstra,, B. Kay,, Suharyono,, A. Budiarson,, A. R. Rifai,, S. S. Wasserman,, G. Losonsky,, J. Kaper,, S. Cryz,, and M. M. Levine. 1993. Studies of the safety, immunogenicity and transmissibility of single-dose live oral cholera vaccine CVD 103-HgR in 24 to 59 month old Indonesian children. J. Infect. Dis. 168: 1169– 1176.
64. Su-Arehawatana, P.,, P. Singharaj,, D. Taylor,, C. Hoge,, A. Trofa,, K. Kuvanont,, S. Migasena,, P. Pitisuttitham,, Y.-L. Lim,, G. Losonsky,, J. B. Kaper,, S. S. Wasserman,, S. Cryz,, P. Echeverria,, and M. M. Levine. 1992. Safety and immunogenicity of different immunization regimens of CVD 103-HgR live oral cholera vaccine in soldiers and civilians in Thailand. J. Infect. Dis. 165: 1042– 1048.
65. Suharyono,, C. Simanjuntak,, N. Witham,, N. Punjabi,, D. G. Heppner,, G. A. Losonsky,, H. Totosudirjo,, A. R. Rifai,, J. Clemens,, Y.-L. Lim,, D. Burr,, S. S. Wasserman,, J. B. Kaper,, K. Sorenson,, S. Cryz,, and M. M. Levine. 1992. Safety and immunogenicity of single-dose live oral cholera vaccine CVD 103-HgR in 5-9-year-old Indonesian children. Lancet 340: 689– 694.
66. Sun, D.,, D. M. Tillman,, T. N. Marion,, and R. K. Taylor. 1990. Production and characterization of monoclonal antibodies to the toxin coregulated pilus (TCP) of Vibrio cholerae that protect against experimental cholera in infant mice. Serodiagn. Immunother. Infect. Dis. 4: 73– 81.
67. Svennerholm, A.-M.,, M. M. Levine,, and J. Holmgren. 1984. Weak serum and intestinal antibody responses to Vibrio cholerae soluble hemagglutinin in cholera patients. Infect. Immun. 45: 792– 794.
68. Tacket, C. O.,, B. Forrest,, R. Morona,, S. R. Attridge,, J. LaBrooy,, B. D. Tall,, M. Reymann,, D. Rowley,, and M. M. Levine. 1990. Safety, immunogenicity, and efficacy against cholera challenge in man of a typhoid-cholera hybrid vaccine derived from Salmonella typhi Ty21a. Infect. Immun. 58: 1620– 1627.
69. Tacket, C. O.,, D. M. Hone,, G. Losonsky,, L. Guers,, R. Edelman,, and M. M. Levine. 1992. Clinical acceptability and immunogenicity of CVD 908 Salmonella typhi vaccine strain. Vaccine 10: 443– 446.
70. Tacket, C. O.,, G. Losonsky,, J. P. Nataro,, S. J. Cryz,, R. Edelman,, A. Fasano,, J. Michalsi,, J. B. Kaper,, and M. M. Levine. Safety, immunogenicity and transmissibility of live oral cholera vaccine candidate CVD 110, a ActxA Azof Aace derivative of El Tor Ogawa Vibrio cholerae. J. Infect. Dis., in press.
71. Tacket, C. O.,, G. Losonsky,, J. Nataro,, S. J. Cryz,, R. Edelman,, J. B. Kaper,, and M. M. Levine. 1992. Rapid onset and duration of protective immunity in challenged volunteers after vaccination with live oral cholera vaccine CVD 103-HgR. J. Infect. Dis. 166: 837– 841.
72. Taylor, D.,, and J. J. Mekalanos. Personal communication.
73. Taylor, R. K.,, C. Shaw,, K. Peterson,, P. Spears,, and J. J. Mekalanos. 1988. Safe, live Vibrio cholerae vaccines. Vaccine 6: 151– 154.
74. Trucksis, M.,, J. E. Galen,, J. Michalski,, A. Fasano,, and J. B. Kaper. 1993. Accessory cholera enterotoxin (Ace), the third member of a Vibrio cholerae virulence cassette. Proc. Natl. Acad. Sci. USA 90: 5267– 5271.
75. Woodward, W. 1971. Cholera reinfection in man. J. Infect. Dis. 123: 61– 66.

References: V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V.