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Infection and Immunity, October 2003, p. 5498-5504, Vol. 71, No. 10
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.10.5498-5504.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Construction and Evaluation of a Safe, Live, Oral Vibrio cholerae Vaccine Candidate, IEM108

Weili Liang, Shixia Wang, Fenggang Yu, Lijuan Zhang, Guoming Qi, Yanqing Liu, Shouyi Gao, and Biao Kan^*

Priority Laboratory of Medical Molecular Bacteriology of the Ministry of Health, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing102206, People's Republic of China

Received 21 March 2003/ Returned for modification 6 May 2003/ Accepted 17 July 2003

IEM101, a Vibrio cholerae O1 El Tor Ogawa strain naturally deficient in CTX, was previously selected as a live cholera vaccine candidate. To make a better and safer vaccine that can induce protective immunity against both the bacteria and cholera toxin (CT), a new vaccine candidate, IEM108, was constructed by introducing a ctxB gene and an El Tor-derived rstR gene into IEM101. The ctxB gene codes for the protective antigen CTB subunit, and the rstR gene mediates phage immunity. The stable expression of the two genes was managed by a chromosome-plasmid lethal balanced system based on the housekeeping gene thyA. Immunization studies indicate that IEM108 generates good immune responses against both the bacteria and CT. After a single-dose intraintestinal vaccination with 10⁹ CFU of IEM108, both anti-CTB immunoglobulin G and vibriocidal antibodies were detected in the immunized-rabbit sera. However, only vibriocidal antibodies are detected in rabbits immunized with IEM101. In addition, IEM108 but not IEM101 conferred full protection against the challenges of four wild-type toxigenic strains of V. cholerae O1 and 4 µg of CT protein in a rabbit model. By introducing the rstR gene, the frequency of conjugative transfer of a recombinant El Tor-derived RS2 suicidal plasmid to IEM108 was decreased 100-fold compared to that for IEM101. This indicated that the El Tor-derived rstR cloned in IEM108 was fully functional and could effectively inhibit the El Tor-derived CTX from infecting IEM108. Our results demonstrate that IEM108 is an efficient and safe live oral cholera vaccine candidate that induces antibacterial and antitoxic immunity and CTX phage immunity.

Editor: D. L. Burns

Present address: Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655.

Present address: National University Medical Institute, National University of Singapore, Clinical Research Center, 117597 Singapore, Singapore.

This article has been cited by other articles:

• Pang, B., Yan, M., Cui, Z., Ye, X., Diao, B., Ren, Y., Gao, S., Zhang, L., Kan, B. (2007). Genetic Diversity of Toxigenic and Nontoxigenic Vibrio cholerae Serogroups O1 and O139 Revealed by Array-Based Comparative Genomic Hybridization. J. Bacteriol. 189: 4837-4849 [Abstract] [Full Text]