Characteristic of K3 (CpG-ODN) as a Transcutaneous Vaccine Formulation Adjuvant
Transcutaneous immunization (TCI) is easy to use, minimally invasive, and has excellent efficacy in vaccines against infections. We focused on toll-like receptor (TLR) ligands as applicable adjuvants for transcutaneous formulations and characterized immune responses. TCI was performed using poke-and...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-03-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/3/267 |
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| author | Sayami Ito Sachiko Hirobe Takuto Kawakita Mio Saito Ying-Shu Quan Fumio Kamiyama Ken J. Ishii Mizuho Nagao Takao Fujisawa Masashi Tachibana Naoki Okada |
| author_facet | Sayami Ito Sachiko Hirobe Takuto Kawakita Mio Saito Ying-Shu Quan Fumio Kamiyama Ken J. Ishii Mizuho Nagao Takao Fujisawa Masashi Tachibana Naoki Okada |
| author_sort | Sayami Ito |
| collection | DOAJ |
| description | Transcutaneous immunization (TCI) is easy to use, minimally invasive, and has excellent efficacy in vaccines against infections. We focused on toll-like receptor (TLR) ligands as applicable adjuvants for transcutaneous formulations and characterized immune responses. TCI was performed using poke-and-patch methods, in which puncture holes are formed with a polyglycolic acid microneedle on the back skin of mice. Various TLR ligands were applied to the puncture holes and covered with an ovalbumin-loaded hydrophilic gel patch. During the screening process, K3 (CpG-oligonucleotide) successfully produced more antigen-specific antibodies than other TLR ligands and induced T helper (Th) 1-type polarization. Transcutaneously administered K3 was detected in draining lymph nodes and was found to promote B cell activation and differentiation, suggesting a direct transcutaneous adjuvant activity on B cells. Furthermore, a human safety test of K3-loaded self-dissolving microneedles (sdMN) was performed. Although a local skin reaction was observed at the sdMN application site, there was no systemic side reaction. In summary, we report a K3-induced Th1-type immune response that is a promising adjuvant for transcutaneous vaccine formulations using MN and show that K3-loaded sdMN can be safely applied to human skin. |
| first_indexed | 2024-04-14T01:13:03Z |
| format | Article |
| id | doaj.art-6e7171d817f94744ab601fe699997f77 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-14T01:13:03Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-6e7171d817f94744ab601fe699997f772022-12-22T02:20:57ZengMDPI AGPharmaceutics1999-49232020-03-0112326710.3390/pharmaceutics12030267pharmaceutics12030267Characteristic of K3 (CpG-ODN) as a Transcutaneous Vaccine Formulation AdjuvantSayami Ito0Sachiko Hirobe1Takuto Kawakita2Mio Saito3Ying-Shu Quan4Fumio Kamiyama5Ken J. Ishii6Mizuho Nagao7Takao Fujisawa8Masashi Tachibana9Naoki Okada10Project for Vaccine and Immune Regulation, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, JapanAdvanced Research of Medical and Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, JapanProject for Vaccine and Immune Regulation, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, JapanCosMED Pharmaceutical Co. Ltd., 32 Higashikujokawanishi-cho, Minami-ku, Kyoto 601-8014, JapanCosMED Pharmaceutical Co. Ltd., 32 Higashikujokawanishi-cho, Minami-ku, Kyoto 601-8014, JapanCosMED Pharmaceutical Co. Ltd., 32 Higashikujokawanishi-cho, Minami-ku, Kyoto 601-8014, JapanDivision of Vaccine Science, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, JapanAllergy Center and Department of Clinical Research, Mie National Hospital, 357 Osato-kubota, Tsu, Mie 514-0125, JapanAllergy Center and Department of Clinical Research, Mie National Hospital, 357 Osato-kubota, Tsu, Mie 514-0125, JapanProject for Vaccine and Immune Regulation, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, JapanProject for Vaccine and Immune Regulation, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, JapanTranscutaneous immunization (TCI) is easy to use, minimally invasive, and has excellent efficacy in vaccines against infections. We focused on toll-like receptor (TLR) ligands as applicable adjuvants for transcutaneous formulations and characterized immune responses. TCI was performed using poke-and-patch methods, in which puncture holes are formed with a polyglycolic acid microneedle on the back skin of mice. Various TLR ligands were applied to the puncture holes and covered with an ovalbumin-loaded hydrophilic gel patch. During the screening process, K3 (CpG-oligonucleotide) successfully produced more antigen-specific antibodies than other TLR ligands and induced T helper (Th) 1-type polarization. Transcutaneously administered K3 was detected in draining lymph nodes and was found to promote B cell activation and differentiation, suggesting a direct transcutaneous adjuvant activity on B cells. Furthermore, a human safety test of K3-loaded self-dissolving microneedles (sdMN) was performed. Although a local skin reaction was observed at the sdMN application site, there was no systemic side reaction. In summary, we report a K3-induced Th1-type immune response that is a promising adjuvant for transcutaneous vaccine formulations using MN and show that K3-loaded sdMN can be safely applied to human skin.https://www.mdpi.com/1999-4923/12/3/267transcutaneous immunizationmicroneedlepoke-and-patchskin vaccinationtranscutaneous drug deliverytlr9 ligandclinical researchsafety test |
| spellingShingle | Sayami Ito Sachiko Hirobe Takuto Kawakita Mio Saito Ying-Shu Quan Fumio Kamiyama Ken J. Ishii Mizuho Nagao Takao Fujisawa Masashi Tachibana Naoki Okada Characteristic of K3 (CpG-ODN) as a Transcutaneous Vaccine Formulation Adjuvant Pharmaceutics transcutaneous immunization microneedle poke-and-patch skin vaccination transcutaneous drug delivery tlr9 ligand clinical research safety test |
| title | Characteristic of K3 (CpG-ODN) as a Transcutaneous Vaccine Formulation Adjuvant |
| title_full | Characteristic of K3 (CpG-ODN) as a Transcutaneous Vaccine Formulation Adjuvant |
| title_fullStr | Characteristic of K3 (CpG-ODN) as a Transcutaneous Vaccine Formulation Adjuvant |
| title_full_unstemmed | Characteristic of K3 (CpG-ODN) as a Transcutaneous Vaccine Formulation Adjuvant |
| title_short | Characteristic of K3 (CpG-ODN) as a Transcutaneous Vaccine Formulation Adjuvant |
| title_sort | characteristic of k3 cpg odn as a transcutaneous vaccine formulation adjuvant |
| topic | transcutaneous immunization microneedle poke-and-patch skin vaccination transcutaneous drug delivery tlr9 ligand clinical research safety test |
| url | https://www.mdpi.com/1999-4923/12/3/267 |
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