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. 1996 Apr;64(4):1454–1457. doi: 10.1128/iai.64.4.1454-1457.1996

Randomized, double-blind placebo-controlled trial to evaluate the safety and immunogenicity of combined Salmonella typhi Ty21a and Vibrio cholerae CVD 103-HgR live oral vaccines.

H Kollaritsch 1, E Furer 1, C Herzog 1, G Wiedermann 1, J U Que 1, S J Cryz Jr 1
PMCID: PMC173943  PMID: 8606118

Abstract

Healthy adults (n=330) were randomized to receive either a bivalent vaccine composed of Vibrio cholerae CVD 103-HgR and Salmonella typhi Ty21a or a placebo. The combined vaccine was well tolerated. Approximately 80% of vaccines manifested a significant rise in anti-S. typhi immunoglobulin G or immunoglobulin A lipopolysaccharide antibody levels. Significant (fourfold or greater) rises in anti-Inaba or anti-Ogawa vibriocidal antibody titer were achieved by 94 and 80% of vaccine recipients, respectively. Elevated baseline vibriocidal antibody titers showed a modest suppressive effect on the rate of seroconversion.

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Selected References

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  1. Barrett P., Clarke P., Cryz S., Jr Oral cholera vaccine well tolerated. BMJ. 1993 Nov 27;307(6916):1425–1425. doi: 10.1136/bmj.307.6916.1425-b. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Clemens J. D., van Loon F., Sack D. A., Chakraborty J., Rao M. R., Ahmed F., Harris J. R., Khan M. R., Yunus M., Huda S. Field trial of oral cholera vaccines in Bangladesh: serum vibriocidal and antitoxic antibodies as markers of the risk of cholera. J Infect Dis. 1991 Jun;163(6):1235–1242. doi: 10.1093/infdis/163.6.1235. [DOI] [PubMed] [Google Scholar]
  3. Clements M. L., Levine M. M., Young C. R., Black R. E., Lim Y. L., Robins-Browne R. M., Craig J. P. Magnitude, kinetics, and duration of vibriocidal antibody responses in North Americans after ingestion of Vibrio cholerae. J Infect Dis. 1982 Apr;145(4):465–473. doi: 10.1093/infdis/145.4.465. [DOI] [PubMed] [Google Scholar]
  4. Cryz S. J., Jr, Levine M. M., Kaper J. B., Fürer E., Althaus B. 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. 1990 Dec;8(6):577–580. doi: 10.1016/0264-410x(90)90012-b. [DOI] [PubMed] [Google Scholar]
  5. Cryz S. J., Jr, Levine M. M., Losonsky G., Kaper J. B., Althaus B. Safety and immunogenicity of a booster dose of Vibrio cholerae CVD 103-HgR live oral cholera vaccine in Swiss adults. Infect Immun. 1992 Sep;60(9):3916–3917. doi: 10.1128/iai.60.9.3916-3917.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cryz S. J., Jr Post-marketing experience with live oral Ty21a vaccine. Lancet. 1993 Jan 2;341(8836):49–50. doi: 10.1016/0140-6736(93)92522-u. [DOI] [PubMed] [Google Scholar]
  7. Cryz S. J., Jr, Que J. U., Levine M. M., Wiedermann G., Kollaritsch H. Safety and immunogenicity of a live oral bivalent typhoid fever (Salmonella typhi Ty21a)-cholera (Vibrio cholerae CVD 103-HgR) vaccine in healthy adults. Infect Immun. 1995 Apr;63(4):1336–1339. doi: 10.1128/iai.63.4.1336-1339.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cryz S. J., Jr, Vanprapar N., Thisyakorn U., Olanratmanee T., Losonsky G., Levine M. M., Chearskul S. Safety and immunogenicity of Salmonella typhi Ty21a vaccine in young Thai children. Infect Immun. 1993 Mar;61(3):1149–1151. doi: 10.1128/iai.61.3.1149-1151.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Glass R. I., Svennerholm A. M., Khan M. R., Huda S., Huq M. I., Holmgren J. Seroepidemiological studies of El Tor cholera in Bangladesh: association of serum antibody levels with protection. J Infect Dis. 1985 Feb;151(2):236–242. doi: 10.1093/infdis/151.2.236. [DOI] [PubMed] [Google Scholar]
  10. Gotuzzo E., Butron B., Seas C., Penny M., Ruiz R., Losonsky G., Lanata C. F., Wasserman S. S., Salazar E., Kaper J. B. Safety, immunogenicity, and excretion pattern of single-dose live oral cholera vaccine CVD 103-HgR in Peruvian adults of high and low socioeconomic levels. Infect Immun. 1993 Sep;61(9):3994–3997. doi: 10.1128/iai.61.9.3994-3997.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kotloff K. L., Wasserman S. S., O'Donnell S., Losonsky G. A., Cryz S. J., Levine M. M. 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. 1992 Oct;60(10):4430–4432. doi: 10.1128/iai.60.10.4430-4432.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Levine M. M., Ferreccio C., Black R. E., Tacket C. O., Germanier R. Progress in vaccines against typhoid fever. Rev Infect Dis. 1989 May-Jun;11 (Suppl 3):S552–S567. doi: 10.1093/clinids/11.supplement_3.s552. [DOI] [PubMed] [Google Scholar]
  13. Levine M. M., Ferreccio C., Cryz S., Ortiz E. Comparison of enteric-coated capsules and liquid formulation of Ty21a typhoid vaccine in randomised controlled field trial. Lancet. 1990 Oct 13;336(8720):891–894. doi: 10.1016/0140-6736(90)92266-k. [DOI] [PubMed] [Google Scholar]
  14. Levine M. M., Herrington D., Murphy J. R., Morris J. G., Losonsky G., Tall B., Lindberg A. A., Svenson S., Baqar S., Edwards M. F. Safety, infectivity, immunogenicity, and in vivo stability of two attenuated auxotrophic mutant strains of Salmonella typhi, 541Ty and 543Ty, as live oral vaccines in humans. J Clin Invest. 1987 Mar;79(3):888–902. doi: 10.1172/JCI112899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Levine M. M., Kaper J. B., Herrington D., Ketley J., Losonsky G., Tacket C. O., Tall B., Cryz S. Safety, immunogenicity, and efficacy of recombinant live oral cholera vaccines, CVD 103 and CVD 103-HgR. Lancet. 1988 Aug 27;2(8609):467–470. doi: 10.1016/s0140-6736(88)90120-1. [DOI] [PubMed] [Google Scholar]
  16. Levine M. M., Kaper J. B. Live oral vaccines against cholera: an update. Vaccine. 1993;11(2):207–212. doi: 10.1016/0264-410x(93)90019-t. [DOI] [PubMed] [Google Scholar]
  17. Olanratmanee T., Levine M., Losonsky G., Thisyakorn V., Cryz S. J., Jr Safety and immunogenicity of Salmonella typhi Ty21a liquid formulation vaccine in 4- to 6-year-old Thai children. J Infect Dis. 1992 Aug;166(2):451–452. doi: 10.1093/infdis/166.2.451. [DOI] [PubMed] [Google Scholar]
  18. Siddique A. K., Salam A., Islam M. S., Akram K., Majumdar R. N., Zaman K., Fronczak N., Laston S. Why treatment centres failed to prevent cholera deaths among Rwandan refugees in Goma, Zaire. Lancet. 1995 Feb 11;345(8946):359–361. doi: 10.1016/s0140-6736(95)90344-5. [DOI] [PubMed] [Google Scholar]
  19. Simanjuntak C. H., O'Hanley P., Punjabi N. H., Noriega F., Pazzaglia G., Dykstra P., Kay B., Suharyono, Budiarso A., Rifai A. R. Safety, immunogenicity, and transmissibility of single-dose live oral cholera vaccine strain CVD 103-HgR in 24- to 59-month-old Indonesian children. J Infect Dis. 1993 Nov;168(5):1169–1176. doi: 10.1093/infdis/168.5.1169. [DOI] [PubMed] [Google Scholar]
  20. Simanjuntak C. H., Paleologo F. P., Punjabi N. H., Darmowigoto R., Soeprawoto, Totosudirjo H., Haryanto P., Suprijanto E., Witham N. D., Hoffman S. L. Oral immunisation against typhoid fever in Indonesia with Ty21a vaccine. Lancet. 1991 Oct 26;338(8774):1055–1059. doi: 10.1016/0140-6736(91)91910-m. [DOI] [PubMed] [Google Scholar]
  21. Suharyono, Simanjuntak C., Witham N., Punjabi N., Heppner D. G., Losonsky G., Totosudirjo H., Rifai A. R., Clemens J., Lim Y. L. Safety and immunogenicity of single-dose live oral cholera vaccine CVD 103-HgR in 5-9-year-old Indonesian children. Lancet. 1992 Sep 19;340(8821):689–694. doi: 10.1016/0140-6736(92)92231-4. [DOI] [PubMed] [Google Scholar]
  22. Tacket C. O., Losonsky G., Nataro J. P., Cryz S. J., Edelman R., Kaper J. B., Levine M. M. Onset and duration of protective immunity in challenged volunteers after vaccination with live oral cholera vaccine CVD 103-HgR. J Infect Dis. 1992 Oct;166(4):837–841. doi: 10.1093/infdis/166.4.837. [DOI] [PubMed] [Google Scholar]
  23. Taylor D. N., Pollard R. A., Blake P. A. Typhoid in the United States and the risk to the international traveler. J Infect Dis. 1983 Sep;148(3):599–602. doi: 10.1093/infdis/148.3.599. [DOI] [PubMed] [Google Scholar]
  24. Threlfall E. J., Said B., Rowe B. Emergence of multiple drug resistance in Vibrio cholerae O1 El Tor from Ecuador. Lancet. 1993 Nov 6;342(8880):1173–1173. doi: 10.1016/0140-6736(93)92156-n. [DOI] [PubMed] [Google Scholar]

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