This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by García, L.
Right arrow Articles by Fando, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by García, L.
Right arrow Articles by Fando, R.

 Previous Article  |  Next Article 

Infection and Immunity, May 2005, p. 3018-3024, Vol. 73, No. 5
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.5.3018-3024.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The Vaccine Candidate Vibrio cholerae 638 Is Protective against Cholera in Healthy Volunteers

Luis García,1,{dagger} Manuel Díaz Jidy,2,{dagger} Hilda García,1 Boris L. Rodríguez,3 Roberto Fernández,2 Gemma Año,1 Bárbara Cedré,1 Tania Valmaseda,1 Edith Suzarte,3 Margarita Ramírez,2 Yadira Pino,1 Javier Campos,3 Jorge Menéndez,1 Rodrigo Valera,1 Daniel González,2 Irma González,1 Oliver Pérez,1 Teresita Serrano,2 Miriam Lastre,1 Fernando Miralles,2 Judith del Campo,1 Jorge Luis Maestre,2 José Luis Pérez,1 Arturo Talavera,1 Antonio Pérez,2 Karen Marrero,3 Talena Ledón,3 and Rafael Fando3*

Instituto Finlay de Sueros y Vacunas, P.O. Box 16017, La Lisa, Ciudad de La Habana, Cuba,1 Instituto de Medicina Tropical Pedro Kouri, P.O. Box 601, La Lisa, Ciudad de La Habana, Cuba,2 Centro Nacional de Investigaciones Científicas, P.O. Box 6412, Playa, Ciudad de La Habana, Cuba3

Received 2 September 2004/ Returned for modification 19 November 2004/ Accepted 17 January 2005

Vibrio cholerae 638 is a living candidate cholera vaccine strain attenuated by deletion of the CTX{Phi} prophage from C7258 (O1, El Tor Ogawa) and by insertion of the Clostridium thermocellum endoglucanase A gene into the hemagglutinin/protease coding sequence. This vaccine candidate was previously found to be well tolerated and immunogenic in volunteers. This article reports a randomized, double-blind, placebo-controlled trial conducted to test short-term protection conferred by 638 against subsequent V. cholerae infection and disease in volunteers in Cuba. A total of 45 subjects were enrolled and assigned to receive vaccine or placebo. The vaccine contained 109 CFU of freshly harvested 638 buffered with 1.3% NaHCO3, while the placebo was buffer alone. After vaccine but not after placebo intake, 96% of volunteers had at least a fourfold increase in vibriocidal antibody titers, and 50% showed a doubling of at least the lipopolysaccharide-specific immunoglobulin A titers in serum. At 1 month after vaccination, five volunteers from the vaccine group and five from the placebo group underwent an exploratory challenge study with 109 CFU of {Delta}CTX{Phi} attenuated mutant strain V. cholerae 81. Only two volunteers from the vaccine group shed strain 81 in their feces, but none of them experienced diarrhea; in the placebo group, all volunteers excreted the challenge strain, and three had reactogenic diarrhea. An additional 12 vaccinees and 9 placebo recipients underwent challenge with 7 x 105 CFU of virulent strain V. cholerae 3008 freshly harvested from a brain heart infusion agar plate and buffered with 1.3% NaHCO3. Three volunteers (25%) from the vaccine group and all from the placebo group shed the challenge agent in their feces. None of the 12 vaccinees but 7 volunteers from the placebo group had diarrhea, and 2 of the latter exhibited severe cholera (>5,000 g of diarrheal stool). These results indicate that at 1 month after ingestion of a single oral dose (109 CFU) of strain 638, volunteers remained protected against cholera infection and disease provoked by the wild-type challenge agent V. cholerae 3008. We recommend that additional vaccine lots of 638 be prepared under good manufacturing practices for further evaluation.

* Corresponding author. Mailing address: Centro Nacional de Investigaciones Científicas, P.O. Box 6412, Avenida 25, Esquina a 158, Ciudad de La Habana, Cuba. Phone: 537 2085 243. Fax: 537 2080 497. E-mail: rafael.fando{at}cnic.edu.cu.

Editor: V. J. DiRita

{dagger} Luis García and Manuel Díaz Jidy contributed equally to the results presented in this article.

Infection and Immunity, May 2005, p. 3018-3024, Vol. 73, No. 5
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.5.3018-3024.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Silva, A. J., Sultan, S. Z., Liang, W., Benitez, J. A. (2008). Role of the Histone-Like Nucleoid Structuring Protein in the Regulation of rpoS and RpoS-Dependent Genes in Vibrio cholerae. J. Bacteriol. 190: 7335-7345 [Abstract] [Full Text]  
  • Schild, S., Nelson, E. J., Camilli, A. (2008). Immunization with Vibrio cholerae Outer Membrane Vesicles Induces Protective Immunity in Mice. Infect. Immun. 76: 4554-4563 [Abstract] [Full Text]  
  • Aebischer, T, Bumann, D, Epple, H J, Metzger, W, Schneider, T, Cherepnev, G, Walduck, A K, Kunkel, D, Moos, V, Loddenkemper, C, Jiadze, I, Panasyuk, M, Stolte, M, Graham, D Y, Zeitz, M, Meyer, T F (2008). Correlation of T cell response and bacterial clearance in human volunteers challenged with Helicobacter pylori revealed by randomised controlled vaccination with Ty21a-based Salmonella vaccines. Gut 57: 1065-1072 [Abstract] [Full Text]  
  • Olivier, V., Haines, G. K. III, Tan, Y., Satchell, K. J. F. (2007). Hemolysin and the Multifunctional Autoprocessing RTX Toxin Are Virulence Factors during Intestinal Infection of Mice with Vibrio cholerae El Tor O1 Strains. Infect. Immun. 75: 5035-5042 [Abstract] [Full Text]  
  • Xicohtencatl-Cortes, J., Lyons, S., Chaparro, A. P., Hernandez, D. R., Saldana, Z., Ledesma, M. A., Rendon, M. A., Gewirtz, A. T., Klose, K. E., Giron, J. A. (2006). Identification of Proinflammatory Flagellin Proteins in Supernatants of Vibrio cholerae O1 by Proteomics Analysis. Mol. Cell. Proteomics 5: 2374-2383 [Abstract] [Full Text]  
  • Silva, A. J., Leitch, G. J., Camilli, A., Benitez, J. A. (2006). Contribution of Hemagglutinin/Protease and Motility to the Pathogenesis of El Tor Biotype Cholera. Infect. Immun. 74: 2072-2079 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»