In vivo and in vitro adjuvant activities of the B subunit of Type IIb heat-labile enterotoxin (LT-IIb-B5) from Escherichia coli |
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Authors: | Shuang Liang Kavita B Hosur Hesham F Nawar Michael W Russell Terry D Connell George Hajishengallis |
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Institution: | 1. Department of Periodontics/Oral Health and Systemic Disease, University of Louisville School of Dentistry, Louisville, KY 40292, USA;2. Department of Microbiology and Immunology, Witebsky Center for Microbial Pathogenesis and Immunology, University at Buffalo, NY 14214, USA;3. Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40292, USA |
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Abstract: | The pentameric B subunit of the Escherichia coli LT-IIb enterotoxin (LT-IIb-B5) activates TLR2 signaling in macrophages. Herein we demonstrate that LT-IIb-B5, in contrast to a TLR2-nonbinding point mutant, induces functional activation of bone marrow-derived dendritic cells and stimulates CD4+ T cell proliferation, activities which suggested that LT-IIb-B5 might function as an adjuvant in vivo. Indeed, in an intranasal mouse immunization model, LT-IIb-B5 augmented specific mucosal and serum antibody responses to a co-administered immunogen, at levels which were almost comparable to those induced by intact LT-IIb holotoxin, a potent but toxic adjuvant. Therefore, LT-IIb-B5 displays useful adjuvant properties which, combined with lack of enterotoxicity and relative stability against degradation, may find application in mucosal vaccines. |
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Keywords: | Heat-labile enterotoxins Mucosal adjuvants Dendritic cells |
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