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    Broadly Protective Shigella Vaccine Based on Type III Secretion Apparatus Proteins

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    PickingW_2012.pdf (2.161Mb)
    Issue Date
    2012-03
    Author
    Martinez-Becerra, Francisco J.
    Kissmann, Julian Michael
    Diaz-McNair, Jovita
    Choudhari, Shyamal P.
    Quick, Amy M.
    Mellado-Sanchez, Gabriela
    Clements, John D.
    Pasetti, Marcela F.
    Picking, Wendy Lynn
    Publisher
    American Society for Microbiology
    Type
    Article
    Article Version
    Scholarly/refereed, publisher version
    Rights
    Copyright © 2012, American Society for Microbiology.
    Metadata
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    Abstract
    Shigella spp. are food- and waterborne pathogens that cause severe diarrheal and dysenteric disease associated with high morbidity and mortality. Individuals most often affected are children under 5 years of age in the developing world. The existence of multiple Shigella serotypes and the heterogenic distribution of pathogenic strains, as well as emerging antibiotic resistance, require the development of a broadly protective vaccine. All Shigella spp. utilize a type III secretion system (TTSS) to initiate infection. The type III secretion apparatus (TTSA) is the molecular needle and syringe that form the energized conduit between the bacterial cytoplasm and the host cell to transport effector proteins that manipulate cellular processes to benefit the pathogen. IpaB and IpaD form a tip complex atop the TTSA needle and are required for pathogenesis. Because they are common to all virulent Shigella spp., they are ideal candidate antigens for a subunit-based, broad-spectrum vaccine. We examined the immunogenicity and protective efficacy of IpaB and IpaD, alone or combined, coadministered with a double mutant heat-labile toxin (dmLT) from Escherichia coli, used as a mucosal adjuvant, in a mouse model of intranasal immunization and pulmonary challenge. Robust systemic and mucosal antibody- and T cell-mediated immunities were induced against both proteins, particularly IpaB. Mice immunized in the presence of dmLT with IpaB alone or IpaB combined with IpaD were fully protected against lethal pulmonary infection with Shigella flexneri and Shigella sonnei. We provide the first demonstration that the Shigella TTSAs IpaB and IpaD are promising antigens for the development of a cross-protective Shigella vaccine.
    URI
    http://hdl.handle.net/1808/21557
    DOI
    https://doi.org/10.1128/IAI.06174-11
    Collections
    • Pharmaceutical Chemistry Scholarly Works [336]
    Citation
    Martinez-Becerra, F. J., Kissmann, J. M., Diaz-McNair, J., Choudhari, S. P., Quick, A. M., Mellado-Sanchez, G., … Picking, W. L. (2012). Broadly Protective Shigella Vaccine Based on Type III Secretion Apparatus Proteins. Infection and Immunity, 80(3), 1222–1231. http://doi.org/10.1128/IAI.06174-11

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    KU Libraries
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    Lawrence, KS 66045
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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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