A Heat-labile Enterotoxin B Subunit Mutant (LTB26) of Escherichia coli Enhances Mucosal Immune adjuvanticity via Increased BCR Activity

AbstractHeat-labile enterotoxin B subunit (LTB) of Escherichia coli is a potential mucosal immune adjuvant for its safety. However, the weaker adjuvant activity fails to meet the clinical requirement. Here, one of LTB mutant numbered LTB26 is constructed with enhanced mucosal immune adjuvanticity than that of LTB wild type (LTB). The transcriptome analysis data suggest that LTB26 enhances mucosal immune adjuvanticity via increased expression of BCR and MHC II+ molecular. Furthermore, LTB26 can promote both Th1 and Th2 cell mediated immunity via upregulated expression of IL-4 and IFN-γ. Flow cytometry analysis confirms that LTB26 significantly upregulates the activity of antigen presenting cells (DCs and mature macrophage) compared with LTB and LTB57 mutant. The result demonstrates that LTB26 is a potent mucosal immune adjuvant meeting clinical requirement. The GM1 ganglioside (GM1) binding activity of LTB57 is higher than that of LTB26; instead, the immune adjuvanticity of LTB57 is lower than that of LTB26. The result highlights that the immune adjuvanticity of LTB and its mutant are not positively associated with GM1 affinity, which upends decades understanding of the relationship of LTB adjuvanticity and GM1-binding affinity.

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Attenuated Salmonella Gallinarum secreting an Escherichia coli heat-labile enterotoxin B subunit protein as an adjuvant for oral vaccination against fowl typhoid

Veterinary Immunology and Immunopathology ◽

10.1016/j.vetimm.2012.09.006 ◽

2012 ◽

Vol 150 (3-4) ◽

pp. 149-160 ◽

Cited By ~ 9

Author(s):

Byung Woo Jeon ◽

Chetan V. Jawale ◽

Seung Hwan Kim ◽

John Hwa Lee

Keyword(s):

Escherichia Coli ◽

Oral Vaccination ◽

Salmonella Gallinarum ◽

Subunit Protein ◽

B Subunit ◽

Heat Labile ◽

Fowl Typhoid ◽

Enterotoxin B

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Tissue culture and expression of Escherichia coli heat-labile enterotoxin B subunit in transgenic Peperomia pellucida

Protein Expression and Purification ◽

10.1016/j.pep.2010.02.010 ◽

2010 ◽

Vol 72 (1) ◽

pp. 82-86 ◽

Cited By ~ 11

Author(s):

Nguyen Hoang Loc ◽

Nguyen Hoang Bach ◽

Tae-Geum Kim ◽

Moon-Sik Yang

Keyword(s):

Escherichia Coli ◽

Tissue Culture ◽

B Subunit ◽

Heat Labile ◽

Enterotoxin B

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Escherichia coli Heat-Labile Enterotoxin B Subunit Is a More Potent Mucosal Adjuvant than Its Closely Related Homologue, the B Subunit of Cholera Toxin

Infection and Immunity ◽

10.1128/iai.69.5.3476-3482.2001 ◽

2001 ◽

Vol 69 (5) ◽

pp. 3476-3482 ◽

Cited By ~ 57

Author(s):

Douglas G. Millar ◽

Timothy R. Hirst ◽

Denis P. Snider

Keyword(s):

Escherichia Coli ◽

Cholera Toxin ◽

Lymphocyte Proliferation ◽

Vaccine Adjuvants ◽

B Subunit ◽

Heat Labile ◽

Antibody Titers ◽

Enterotoxin B ◽

Draining Lymph Nodes ◽

Stimulation Of

ABSTRACT Although cholera toxin (Ctx) and Escherichia coliheat-labile enterotoxin (Etx) are known to be potent mucosal adjuvants, it remains controversial whether the adjuvanticity of the holotoxins extends to their nontoxic, receptor-binding B subunits. Here, we have systematically evaluated the comparative adjuvant properties of highly purified recombinant EtxB and CtxB. EtxB was found to be a more potent adjuvant than CtxB, stimulating responses to hen egg lysozyme when the two were coadministered to mice intranasally, as assessed by enhanced serum and secretory antibody titers as well as by stimulation of lymphocyte proliferation in spleen and draining lymph nodes. These results indicate that, although structurally very similar, EtxB and CtxB have strikingly different immunostimulatory properties and should not be considered equivalent as prospective vaccine adjuvants.

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