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Infection and Immunity, November 2000, p. 6411-6418, Vol. 68, No. 11
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Construction and Characterization of a Nonproliferative El Tor Cholera Vaccine Candidate Derived from Strain 638

Edgar Valle,1 Talena Ledón,1 Bárbara Cedré,2 Javier Campos,1 Tania Valmaseda,2 Boris Rodríguez,1 Luis García,2 Karen Marrero,1 Jorge Benítez,1 Sandra Rodríguez,1 and Rafael Fando1,*

Grupo de Genética, Centro Nacional de Investigaciones Científicas,1 and Instituto Finlay, Sueros y Vacunas,2 Havana, Cuba

Received 15 February 2000/Returned for modification 3 April 2000/Accepted 28 July 2000

In recent clinical assays, our cholera vaccine candidate strain, Vibrio cholerae 638 El Tor Ogawa, was well tolerated and immunogenic in Cuban volunteers. In this work we describe the construction of 638T, a thymidine auxotrophic version of improved environmental biosafety. In so doing, the thyA gene from V. cholerae was cloned, sequenced, mutated in vitro, and used to replace the wild-type allele. Except for its dependence on thymidine for growth in minimal medium, 638T is essentially indistinguishable from 638 in the rate of growth and morphology in complete medium. The two strains showed equivalent phenotypes with regard to motility, expression of the celA marker, colonization capacity in the infant mouse cholera model, and immunogenicity in the adult rabbit cholera model. However, the ability of this new strain to survive environmental starvation was limited with respect to that of 638. Taken together, these results suggest that this live, attenuated, but nonproliferative strain is a new, promising cholera vaccine candidate.

* Corresponding author. Mailing address: Centro Nacional de Investigaciones Científicas, AP 6990, Ciudad de La Habana, Cuba. Phone: 537 218066, ext. 248. Fax: 537 330497. E-mail: Fando{at}biocnic.cneuro.edu.cu.

Infection and Immunity, November 2000, p. 6411-6418, Vol. 68, No. 11
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Kotton, C. N., Hohmann, E. L. (2004). Enteric Pathogens as Vaccine Vectors for Foreign Antigen Delivery. Infect. Immun. 72: 5535-5547 [Full Text]  
  • Campos, J., Martinez, E., Suzarte, E., Rodriguez, B. L., Marrero, K., Silva, Y., Ledon, T., del Sol, R., Fando, R. (2003). VGJ{phi}, a Novel Filamentous Phage of Vibrio cholerae, Integrates into the Same Chromosomal Site as CTX{phi}. J. Bacteriol. 185: 5685-5696 [Abstract] [Full Text]  
  • Dougan, G., Huett, A., Clare, S. (2002). Vaccines against human enteric bacterial pathogens. Br Med Bull 62: 113-123 [Abstract] [Full Text]  


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