Next Article in Journal
Crotoxin Conjugated to SBA-15 Nanostructured Mesoporous Silica Induces Long-Last Analgesic Effect in the Neuropathic Pain Model in Mice
Next Article in Special Issue
Nature-Identical Compounds and Organic Acids Reduce E. coli K88 Growth and Virulence Gene Expression In Vitro
Previous Article in Journal
Helicobacter pylori Virulence Factors Exploiting Gastric Colonization and its Pathogenicity
Previous Article in Special Issue
Genotypes, Enterotoxin Gene Profiles, and Antimicrobial Resistance of Staphylococcus aureus Associated with Foodborne Outbreaks in Hangzhou, China
Article

Repeated Oral Administration of a KDEL-Tagged Recombinant Cholera Toxin B Subunit Effectively Mitigates DSS Colitis despite a Robust Immunogenic Response

1
James Graham Brown Cancer Center, Center for Predictive Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA
2
Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA
*
Author to whom correspondence should be addressed.
Received: 21 October 2019 / Revised: 18 November 2019 / Accepted: 19 November 2019 / Published: 20 November 2019
(This article belongs to the Collection Bacterial Enterotoxins)
Cholera toxin B subunit (CTB), a non-toxic homopentameric component of Vibrio cholerae holotoxin, is an oral cholera vaccine antigen that induces an anti-toxin antibody response. Recently, we demonstrated that a recombinant CTB variant with a Lys-Asp-Glu-Leu (KDEL) endoplasmic reticulum retention motif (CTB-KDEL) exhibits colon mucosal healing effects that have therapeutic implications for inflammatory bowel disease (IBD). Herein, we investigated the feasibility of CTB-KDEL for the treatment of chronic colitis. We found that weekly oral administration of CTB-KDEL, dosed before or after the onset of chronic colitis, induced by repeated dextran sodium sulfate (DSS) exposure, could significantly reduce disease activity index scores, intestinal permeability, inflammation, and histological signs of chronicity. To address the consequences of immunogenicity, mice (C57BL/6 or C3H/HeJ strains) were pre-exposed to CTB-KDEL then subjected to DSS colitis and CTB-KDEL treatment. While the pre-dosing of CTB-KDEL elicited high-titer anti-drug antibodies (ADAs) of the immunoglobin A (IgA) isotype in the intestine of C57BL/6 mice, the therapeutic effects of CTB-KDEL were similar to those observed in C3H/HeJ mice, which showed minimal ADAs under the same experimental conditions. Thus, the immunogenicity of CTB-KDEL does not seem to impede the protein’s mucosal healing efficacy. These results support the development of CTB-KDEL for IBD therapy. View Full-Text
Keywords: cholera toxin B subunit; DSS colitis; IBD; immunogenicity cholera toxin B subunit; DSS colitis; IBD; immunogenicity
Show Figures

Figure 1

MDPI and ACS Style

Royal, J.M.; Reeves, M.A.; Matoba, N. Repeated Oral Administration of a KDEL-Tagged Recombinant Cholera Toxin B Subunit Effectively Mitigates DSS Colitis despite a Robust Immunogenic Response. Toxins 2019, 11, 678. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins11120678

AMA Style

Royal JM, Reeves MA, Matoba N. Repeated Oral Administration of a KDEL-Tagged Recombinant Cholera Toxin B Subunit Effectively Mitigates DSS Colitis despite a Robust Immunogenic Response. Toxins. 2019; 11(12):678. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins11120678

Chicago/Turabian Style

Royal, Joshua M., Micaela A. Reeves, and Nobuyuki Matoba. 2019. "Repeated Oral Administration of a KDEL-Tagged Recombinant Cholera Toxin B Subunit Effectively Mitigates DSS Colitis despite a Robust Immunogenic Response" Toxins 11, no. 12: 678. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins11120678

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop