4.5 Article

In vivo and in vitro adjuvant activities of the B subunit of Type IIb heat-labile enterotoxin (LT-IIb-B5) from Escherichia coli

Journal

VACCINE
Volume 27, Issue 32, Pages 4302-4308

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2009.05.027

Keywords

Heat-labile enterotoxins; Mucosal adjuvants; Dendritic cells

Funding

  1. National Institutes of Health [DE13833, DE06746, DE015254, DE017138]

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The pentameric B subunit of the Escherichia coli LT-IIb enterotoxin (LT-IIb-B-5) activates TLR2 signaling in macrophages. Herein we demonstrate that LT-IIb-B-5, 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-B-5 might function as an adjuvant in vivo. Indeed, in an intranasal mouse immunization model, LT-IIb-B-5 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-B-5 displays useful adjuvant properties which, combined with lack of enterotoxicity and relative stability against degradation, may find application in mucosal vaccines. (C) 2009 Elsevier Ltd. All rights reserved.

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