A Vibrio cholerae serogroup O1 vaccine candidate against CTXETΦ infection

Yan, Mei; Liu, Guangwen; Diao, Baowei; Qiu, Haiyan; Zhang, Lijuan; Liang, Weili; Gao, Shouyi; Kan, Biao

doi:10.1016/j.vaccine.2007.02.043

Cited by 6 publications

(9 citation statements)

References 29 publications

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“…Variable gene sequences of pIII CTX have also been documented (9,11). The tcpA sequence of nontoxigenic strain 7743 (also known as IEM101) used in this study is identical to the sequence of seventh-pandemic El Tor strains, and the attB site for CTX⌽ genome integration is also identical (57). Strain 7743 can be infected by CTX ET ⌽ and thereby converted into a toxigenic strain (37,38,57).…”

Section: Discussionmentioning

confidence: 83%

“…The tcpA sequence of nontoxigenic strain 7743 (also known as IEM101) used in this study is identical to the sequence of seventh-pandemic El Tor strains, and the attB site for CTX⌽ genome integration is also identical (57). Strain 7743 can be infected by CTX ET ⌽ and thereby converted into a toxigenic strain (37,38,57). Moreover, rabbits immunized with 7743 and the live-vaccine candidates developed from 7743 can be protected against a challenge with classical or El Tor strains (37)(38)(39)57).…”

Section: Discussionmentioning

confidence: 97%

“…Strain 7743 can be infected by CTX ET ⌽ and thereby converted into a toxigenic strain (37,38,57). Moreover, rabbits immunized with 7743 and the live-vaccine candidates developed from 7743 can be protected against a challenge with classical or El Tor strains (37)(38)(39)57). This protection demonstrates that strain 7743 has the same immunogenicity as toxigenic El Tor strains.…”

Section: Discussionmentioning

confidence: 98%

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Genetic Diversity of Toxigenic and Nontoxigenic Vibrio cholerae Serogroups O1 and O139 Revealed by Array-Based Comparative Genomic Hybridization

et al. 2007

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Toxigenic serogroups O1 and O139 of Vibrio cholerae may cause cholera epidemics or pandemics. Nontoxigenic strains within these serogroups also exist in the environment, and also some may cause sporadic cases of disease. Herein, we investigate the genomic diversity among toxigenic and nontoxigenic O1 and O139 strains by comparative genomic microarray hybridization with the genome of El Tor strain N16961 as a base. Conservation of the toxigenic O1 El Tor and O139 strains is found as previously reported, whereas accumulation of genome changes was documented in toxigenic El Tor strains isolated within the 40 years of the seventh pandemic. High phylogenetic diversity in nontoxigenic O1 and O139 strains is observed, and most of the genes absent from nontoxigenic strains are clustered together in the N16961 genome. By comparing these toxigenic and nontoxigenic strains, we observed that the small chromosome of V. cholerae is quite conservative and stable, outside of the superintegron region. In contrast to the general stability of the genome, the superintegron demonstrates pronounced divergence among toxigenic and nontoxigenic strains. Additionally, sequence variation in virulence-related genes is found in nontoxigenic El Tor strains, and we speculate that these intermediate strains may have pathogenic potential should they acquire CTX prophage alleles and other gene clusters. This genome-wide comparison of toxigenic and nontoxigenic V. cholerae strains may promote understanding of clonal differentiation of V. cholerae and contribute to an understanding of the origins and clonal selection of epidemic strains.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 98%

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Genetic Diversity of Toxigenic and Nontoxigenic Vibrio cholerae Serogroups O1 and O139 Revealed by Array-Based Comparative Genomic Hybridization

et al. 2007

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“…Second, the genomic analysis of emerging strains may be useful when evaluating the efficacy of vaccines and in their design. For example, O1 vaccine strains and strategies utilize expression and secretion of the nontoxic CtxB subunit to enhance efficacy (Thungapathra et al 1999; Jani et al 2002; Liang et al 2003; Qadri et al 2007; Yan et al 2007). There is an emergence of the strains that encode classical-El Tor CTX islands with unique variants in the ctxB gene.…”

Section: Application Of Genomicsmentioning

confidence: 99%

Genomic Science in Understanding Cholera Outbreaks and Evolution of Vibrio cholerae as a Human Pathogen

Robins

Mekalanos

2014

Cholera Outbreaks

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Modern genomic and bioinformatic approaches have been applied to interrogate the V. cholerae genome, the role of genomic elements in cholera disease, and the origin, relatedness, and dissemination of epidemic strains. A universal attribute of choleragenic strains includes a repertoire of pathogenicity islands and virulence genes, namely the CTX–ϕ prophage and Toxin Co-regulated Pilus (TCP) in addition to other virulent genetic elements including those referred to as Seventh Pandemic Islands. During the last decade, the advent of Next Generation Sequencing (NGS) has provided highly resolved and often complete genomic sequences of epidemic isolates in addition to both clinical and environmental strains isolated from geographically unconnected regions. Genomic comparisons of these strains, as was completed during and following the Haitian outbreak in 2010, reveals that most epidemic strains appear closely related, regardless of region of origin. Non-O1 clinical or environmental strains may also possess some virulence islands, but phylogenic analysis of the core genome suggests they are more diverse and distantly related than those isolated during epidemics. Like Haiti, genomic studies that examine both the Vibrio core- and pan-genome in addition to Single Nucleotide Polymorphisms (SNPs) conclude that a number of epidemics are caused by strains that closely resemble those in Asia, and often appear to originate there and then spread globally. The accumulation of SNPs in the epidemic strains over time can then be applied to better understand the evolution of the V. cholerae genome as an etiological agent.

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“…Cholera can spread rapidly and remains a global threat to countries with poor water sanitations (Yan et al . )…”

Section: Introductionmentioning

confidence: 99%

Investigation into immunological responses against a native recombinant CTB whole-cell Vibrio cholerae vaccine in a rabbit model

2012

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Aim: The aim of this study was to express and purify the recombinant CTB (rCTB) protein from Vibrio cholerae and investigate the biological and immunological characteristics of purified protein in rabbit animal model and in combination with Iranian inactivated V. cholerae whole cells as a domestic recombinant WC-CTB vaccine. Methods and Results: Expressed 6XHis-tagged rCTB was properly purified, and its identity was confirmed by Western blotting using cholera toxin-specific antibody. Concentration of purified protein was assessed to be 700 mg l À1 .GM 1 -ELISA assay showed that purified rCTB pentamer was functionally active and able to bind GM 1 in a dose-dependent manner. Recombinant CTB was inoculated into rabbits through intestinal rout alone and in combination with inactivated whole-cell V. cholerae strains (WC). The anti-CTB IgG titre showed that serum IgG responses were significantly increased in groups immunized with rCTB mixed with inactivated WC in comparison with control group. Furthermore, rCTB without V. cholerae WC also stimulated the IgG responses when inoculated into rabbit intestine. Challenge experiments of immunized rabbits showed an adequate protection against V. cholerae strains. Conclusions: Recombinant CTB alone and in combination with inactivated Iranian strains was protective against live toxigenic V. cholerae strains, made it a potential candidate for an indigenous vaccine. Significance and Impact of the Study: It was proved that rCTB produced in this system can be used as a potent immunogenic protein to stimulate the immunity against V. cholerae strains and can be used for developing a native vaccine composed of our local strains with their own surface structures and antigenic determinants against cholera.

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A Vibrio cholerae serogroup O1 vaccine candidate against CTXETΦ infection

Cited by 6 publications

References 29 publications

Genetic Diversity of Toxigenic and Nontoxigenic Vibrio cholerae Serogroups O1 and O139 Revealed by Array-Based Comparative Genomic Hybridization

Genetic Diversity of Toxigenic and Nontoxigenic Vibrio cholerae Serogroups O1 and O139 Revealed by Array-Based Comparative Genomic Hybridization

Genomic Science in Understanding Cholera Outbreaks and Evolution of Vibrio cholerae as a Human Pathogen

Investigation into immunological responses against a native recombinant CTB whole-cell Vibrio cholerae vaccine in a rabbit model

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