Development of Safe and Non-Self-Immunogenic Mucosal Adjuvant by Recombinant Fusion of Cholera Toxin A1 Subunit with Protein Transduction Domain
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...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2018/9830701 |
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| author | Byoung-Shik Shim In Su Cheon Eugene Lee Sung-Moo Park Youngjoo Choi Dae-Im Jung Eunji Yang Jung-ah Choi June Young Chun Jae-Ouk Kim Cheol-Heui Yun Cecil Czerkinsky Man Ki Song |
| author_facet | Byoung-Shik Shim In Su Cheon Eugene Lee Sung-Moo Park Youngjoo Choi Dae-Im Jung Eunji Yang Jung-ah Choi June Young Chun Jae-Ouk Kim Cheol-Heui Yun Cecil Czerkinsky Man Ki Song |
| author_sort | Byoung-Shik Shim |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7d69a1718ec949bcb03472ee0af2459b |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-7d69a1718ec949bcb03472ee0af2459b2025-02-03T05:55:18ZengWileyJournal of Immunology Research2314-88612314-71562018-01-01201810.1155/2018/98307019830701Development of Safe and Non-Self-Immunogenic Mucosal Adjuvant by Recombinant Fusion of Cholera Toxin A1 Subunit with Protein Transduction DomainByoung-Shik Shim0In Su Cheon1Eugene Lee2Sung-Moo Park3Youngjoo Choi4Dae-Im Jung5Eunji Yang6Jung-ah Choi7June Young Chun8Jae-Ouk Kim9Cheol-Heui Yun10Cecil Czerkinsky11Man Ki Song12Laboratory Science Division, International Vaccine Institute, Seoul 08826, Republic of KoreaLaboratory Science Division, International Vaccine Institute, Seoul 08826, Republic of KoreaLaboratory Science Division, International Vaccine Institute, Seoul 08826, Republic of KoreaLaboratory Science Division, International Vaccine Institute, Seoul 08826, Republic of KoreaLaboratory Science Division, International Vaccine Institute, Seoul 08826, Republic of KoreaLaboratory Science Division, International Vaccine Institute, Seoul 08826, Republic of KoreaLaboratory Science Division, International Vaccine Institute, Seoul 08826, Republic of KoreaLaboratory Science Division, International Vaccine Institute, Seoul 08826, Republic of KoreaLaboratory Science Division, International Vaccine Institute, Seoul 08826, Republic of KoreaLaboratory Science Division, International Vaccine Institute, Seoul 08826, Republic of KoreaDepartment of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of KoreaInstitut de Pharmacologie Moleculaire et Cellulaire, CNRS-INSERM-University of Nice-Sophia Antipolis, Valbonne, FranceLaboratory Science Division, International Vaccine Institute, Seoul 08826, Republic of KoreaPotential 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.http://dx.doi.org/10.1155/2018/9830701 |
| spellingShingle | Byoung-Shik Shim In Su Cheon Eugene Lee Sung-Moo Park Youngjoo Choi Dae-Im Jung Eunji Yang Jung-ah Choi June Young Chun Jae-Ouk Kim Cheol-Heui Yun Cecil Czerkinsky Man Ki Song Development of Safe and Non-Self-Immunogenic Mucosal Adjuvant by Recombinant Fusion of Cholera Toxin A1 Subunit with Protein Transduction Domain Journal of Immunology Research |
| title | Development of Safe and Non-Self-Immunogenic Mucosal Adjuvant by Recombinant Fusion of Cholera Toxin A1 Subunit with Protein Transduction Domain |
| title_full | Development of Safe and Non-Self-Immunogenic Mucosal Adjuvant by Recombinant Fusion of Cholera Toxin A1 Subunit with Protein Transduction Domain |
| title_fullStr | Development of Safe and Non-Self-Immunogenic Mucosal Adjuvant by Recombinant Fusion of Cholera Toxin A1 Subunit with Protein Transduction Domain |
| title_full_unstemmed | Development of Safe and Non-Self-Immunogenic Mucosal Adjuvant by Recombinant Fusion of Cholera Toxin A1 Subunit with Protein Transduction Domain |
| title_short | Development of Safe and Non-Self-Immunogenic Mucosal Adjuvant by Recombinant Fusion of Cholera Toxin A1 Subunit with Protein Transduction Domain |
| title_sort | development of safe and non self immunogenic mucosal adjuvant by recombinant fusion of cholera toxin a1 subunit with protein transduction domain |
| url | http://dx.doi.org/10.1155/2018/9830701 |
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