In vivo and in vitro adjuvant activities of the B subunit of Type IIb heat-labile enterotoxin (LT-IIb-B5) from Escherichia coli.
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.
Liang
Shuang
S
Department of Periodontics/Oral Health and Systemic Disease, University of Louisville School of Dentistry, Louisville, KY 40292, USA.
Hosur
Kavita B
KB
Nawar
Hesham F
HF
Russell
Michael W
MW
Connell
Terry D
TD
Hajishengallis
George
G
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000281:Administration, Intranasal; D000818:Animals; D000906:Antibodies / Q000032:analysis / Q000097:blood; D001427:Bacterial Toxins / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004768:Enterotoxins / Q000494:pharmacology*; D029968:Escherichia coli Proteins / Q000494:pharmacology*; D018928:Immunity, Mucosal; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D021122:Protein Subunits / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000906:Antibodies; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D021122:Protein Subunits; C027538:heat-labile enterotoxin, E coli