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    Characterization of a Novel Fusion Protein from IpaB and IpaD of Shigella spp. and Its Potential as a Pan-Shigella Vaccine

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    Picking_2013.pdf (1.183Mb)
    Issue Date
    2013-12
    Author
    Martinez-Becerra, Francisco J.
    Chen, Xiaotong
    Dickenson, Nicholas E.
    Choudhari, Shyamal P.
    Harrison, Kelly
    Clements, John D.
    Picking, William D.
    Van De Verg, Lillian L.
    Walker, Richard I.
    Picking, Wendy Lynn
    Publisher
    American Society for Microbiology
    Type
    Article
    Article Version
    Scholarly/refereed, publisher version
    Rights
    Copyright © 2013, American Society for Microbiology. All Rights Reserved.
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    Abstract
    Shigellosis is an important disease in the developing world, where about 90 million people become infected with Shigella spp. each year. We previously demonstrated that the type three secretion apparatus (T3SA) proteins IpaB and IpaD are protective antigens in the mouse lethal pulmonary model. In order to simplify vaccine formulation and process development, we have evaluated a vaccine design that incorporates both of these previously tested Shigella antigens into a single polypeptide chain. To determine if this fusion protein (DB fusion) retains the antigenic and protective capacities of IpaB and IpaD, we immunized mice with the DB fusion and compared the immune response to that elicited by the IpaB/IpaD combination vaccine. Purification of the DB fusion required coexpression with IpgC, the IpaB chaperone, and after purification it maintained the highly α-helical characteristics of IpaB and IpaD. The DB fusion also induced comparable immune responses and retained the ability to protect mice against Shigella flexneri and S. sonnei in the lethal pulmonary challenge. It also offered limited protection against S. dysenteriae challenge. Our results show the feasibility of generating a protective Shigella vaccine comprised of the DB fusion.
    URI
    http://hdl.handle.net/1808/21320
    DOI
    https://doi.org/10.1128/IAI.00859-13
    Collections
    • Pharmaceutical Chemistry Scholarly Works [353]
    Citation
    Martinez-Becerra, F. J., Chen, X., Dickenson, N. E., Choudhari, S. P., Harrison, K., Clements, J. D., … Picking, W. L. (2013). Characterization of a Novel Fusion Protein from IpaB and IpaD of Shigella spp. and Its Potential as a Pan-Shigella Vaccine. Infection and Immunity, 81(12), 4470–4477. http://doi.org/10.1128/IAI.00859-13

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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