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Open AccessArticle

Characteristic of K3 (CpG-ODN) as a Transcutaneous Vaccine Formulation Adjuvant

1
Project for Vaccine and Immune Regulation, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan
2
Advanced Research of Medical and Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan
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Project of Clinical Pharmacology and Therapeutics, Center for Advanced Education and Research in Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan
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Department of Molecular Pharmaceutical Science, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
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CosMED Pharmaceutical Co. Ltd., 32 Higashikujokawanishi-cho, Minami-ku, Kyoto 601-8014, Japan
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Division of Vaccine Science, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
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Allergy Center and Department of Clinical Research, Mie National Hospital, 357 Osato-kubota, Tsu, Mie 514-0125, Japan
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Laboratory of Vaccine and Immune Regulation (BIKEN), Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan
*
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(3), 267; https://doi.org/10.3390/pharmaceutics12030267
Received: 19 February 2020 / Revised: 6 March 2020 / Accepted: 13 March 2020 / Published: 15 March 2020
(This article belongs to the Special Issue Advances in Microneedle-Based Drug Delivery Systems)
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. View Full-Text
Keywords: transcutaneous immunization; microneedle; poke-and-patch; skin vaccination; transcutaneous drug delivery; TLR9 ligand; clinical research; safety test transcutaneous immunization; microneedle; poke-and-patch; skin vaccination; transcutaneous drug delivery; TLR9 ligand; clinical research; safety test
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MDPI and ACS Style

Ito, S.; Hirobe, S.; Kawakita, T.; Saito, M.; Quan, Y.-S.; Kamiyama, F.; Ishii, K.J.; Nagao, M.; Fujisawa, T.; Tachibana, M.; Okada, N. Characteristic of K3 (CpG-ODN) as a Transcutaneous Vaccine Formulation Adjuvant. Pharmaceutics 2020, 12, 267.

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