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Journal of Immunology Research
Volume 2018, Article ID 9830701, 11 pages
https://doi.org/10.1155/2018/9830701
Research Article

Development of Safe and Non-Self-Immunogenic Mucosal Adjuvant by Recombinant Fusion of Cholera Toxin A1 Subunit with Protein Transduction Domain

1Laboratory Science Division, International Vaccine Institute, Seoul 08826, Republic of Korea
2Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea
3Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
4Institut de Pharmacologie Moleculaire et Cellulaire, CNRS-INSERM-University of Nice-Sophia Antipolis, Valbonne, France

Correspondence should be addressed to Man Ki Song; tni.ivi@gnoskm

Received 21 July 2017; Revised 3 December 2017; Accepted 10 December 2017; Published 7 March 2018

Academic Editor: Ethan M. Shevach

Copyright © 2018 Byoung-Shik Shim et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Potential use of cholera toxin (CT) as a mucosal vaccine adjuvant has been documented in a variety of animal models. However, native CT is highly toxic to be used as a mucosal adjuvant in humans. Here, we demonstrate a new approach to generate a mucosal adjuvant by replacing the B subunit of CT with HIV-1 Tat protein transduction domain (PTD), which efficiently delivers fusion proteins into the cell cytoplasm by unspecific binding to cell surface. We compared the adjuvanticity and toxicity of Tat PTD-CTA1-Tat PTD (TCTA1T) with those of CT. Our results indicate that intranasal (i.n.) delivery of ovalbumin (OVA) with TCTA1T significantly augments the OVA-specific systemic and mucosal antibody responses to levels comparable to those seen with CT adjuvant. Moreover, in vivo cytotoxic T lymphocyte activity elicited by TCTA1T was significantly higher than that elicited by a mutant TCTA1T (TmCTA1T) lacking ADP-ribosyltransferase function. In addition, coadministration of influenza M2 protein with TCTA1T conferred near complete protection against lethal influenza virus challenge. Importantly, TCTA1T, in contrast to CT, did not induce serum IgG antibody responses to itself and was shown to be nontoxic. These results suggest that TCTA1T may be a safe and effective adjuvant when given by mucosal routes.