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dc.contributor.authorMartinez-Becerra, Francisco J.
dc.contributor.authorKissmann, Julian Michael
dc.contributor.authorDiaz-McNair, Jovita
dc.contributor.authorChoudhari, Shyamal P.
dc.contributor.authorQuick, Amy M.
dc.contributor.authorMellado-Sanchez, Gabriela
dc.contributor.authorClements, John D.
dc.contributor.authorPasetti, Marcela F.
dc.contributor.authorPicking, Wendy Lynn
dc.identifier.citationMartinez-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.
dc.description.abstractShigella 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.en_US
dc.publisherAmerican Society for Microbiologyen_US
dc.rightsCopyright © 2012, American Society for Microbiology.en_US
dc.titleBroadly Protective Shigella Vaccine Based on Type III Secretion Apparatus Proteinsen_US
kusw.kuauthorPicking, Wendy Lynn
kusw.kudepartmentPharmaceutical Chemistryen_US
kusw.oanotesPer SHERPA/RoMEO 9/21/2016: Author's Pre-print: green tick author can archive pre-print (ie pre-refereeing) Author's Post-print: green tick author can archive post-print (ie final draft post-refereeing) Publisher's Version/PDF: green tick author can archive publisher's version/PDF General Conditions:

Author's pre-print on recognised non profit pre-print archives Author's post-print on funder's repositories, institutional repository or subject-based repositories Non-commercial Publisher's version/PDF may be used Publisher's version/PDF may be used on author's personal website or employers website Recommended that author's post-prints submitted to PubMed or institutional repositories are made available 6 months after publication Author's pre-print must be updated with citation and DOI upon publication
kusw.oaversionScholarly/refereed, publisher versionen_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US

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