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    Experimental infection of human volunteers with the heat-stable enterotoxin-producing enterotoxigenic Escherichia coli strain TW11681

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    Author
    Sakkestad, Sunniva Todnem
    Steinsland, Hans
    Barry, Eileen M.
    Date
    2019-06-01
    Journal
    Pathogens
    Publisher
    MDPI AG
    Type
    Article
    
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    Show full item record
    See at
    https://doi.org/10.3390/pathogens8020084
    Abstract
    Infection with enterotoxigenic Escherichia coli (ETEC) producing the heat-stable enterotoxin (ST) is one of the most important causes of childhood diarrhoea in low-and middle-income countries. Here, we undertook a controlled human infection model (CHIM) study to investigate whether ST-producing ETEC strain TW11681 would be suitable for testing the protective efficacy of new ST-based vaccine candidates in vaccine challenge models. In groups of three, nine volunteers ingested 1 × 106, 1 × 107, or 1 × 108 colony-forming units (CFU) of TW11681. Flow cytometry-based assays were used to measure CD4+ T cell responses and antibody levels targeting virulence factors expressed by the strain. We found that infection with TW11681 elicited few and mild symptoms, including mild diarrhoea in two volunteers, both of whom ingested 1 × 106 CFU. Averaged across all volunteers, the CD4+ T cell responses specific for E. coli YghJ mucinase peaked 10 days after infection (3.2-fold (p = 0.016)), while the CD4+ T cell responses specific for Colonization Factor Antigen I (CFA/I) major fimbrial subunit (CfaB) peaked after 28 days (3.6-fold (p = 0.063)). The serum CfaB-specific anti-IgA and anti-IgG/IgM levels were significantly increased and peaked 3 months after infection. Both remained elevated for the duration of the 12-month follow-up. The corresponding anti-YghJ serological response was strongest after 10 days, although a significant increase was seen only for IgA levels (3.2-fold (p = 0.008)). In conclusion, due to its low diarrhoea attack risk, TW11681 is probably not suitable for testing the efficacy of new vaccines in human challenge studies at doses 1 × 106 to 1 × 108. However, the strain may still be useful in CHIMs for studying ETEC host-pathogen interactions. © 2019 by the authors.
    Keyword
    Colonization Factor Antigen I
    Controlled human challenge model
    Diarrhoea
    Enterotoxigenic Escherichia coli
    Experimental infection
    Heat-stable enterotoxin
    YghJ
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85069642084&origin=inward; http://hdl.handle.net/10713/10267
    ae974a485f413a2113503eed53cd6c53
    10.3390/pathogens8020084
    Scopus Count
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    UMB Open Access Articles 2019

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