Characteristics of immune induction by transcutaneous vaccination using dissolving microneedle patches in mice

Sachiko Hirobe; Ryo Susai; Honoka Takeuchi; Ryosuke Eguchi; Sayami Ito; Ying-Shu Quan; Fumio Kamiyama; Naoki Okada

doi:10.1016/j.ijpharm.2021.120563

Characteristics of immune induction by transcutaneous vaccination using dissolving microneedle patches in mice

Int J Pharm. 2021 May 15:601:120563. doi: 10.1016/j.ijpharm.2021.120563. Epub 2021 Mar 31.

Authors

Sachiko Hirobe¹, Ryo Susai², Honoka Takeuchi², Ryosuke Eguchi², Sayami Ito³, Ying-Shu Quan⁴, Fumio Kamiyama⁴, Naoki Okada⁵

Affiliations

¹ Laboratory of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; Laboratory of Clinical Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; Department of Molecular Pharmaceutical Science, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Department of Pharmacy, Osaka University Hospital, 2-15 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: hirobe-s@phs.osaka-u.ac.jp.
² Laboratory of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
³ Laboratory of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; Project for Vaccine and Immune Regulation, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
⁴ CosMED Pharmaceutical Co. Ltd., 32 Higashikujokawanishi-cho, Minami-ku, Kyoto 601-8014, Japan.
⁵ Laboratory of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; Project for Vaccine and Immune Regulation, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; Laboratory of Vaccine and Immune Regulation (BIKEN), Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: okada@phs.osaka-u.ac.jp.

PMID: 33811967
DOI: 10.1016/j.ijpharm.2021.120563

Abstract

Transcutaneous immunization (TCI) is an appealing vaccination method. Compared with conventional injectable immunization, TCI is easier and less painful. We previously developed a dissolving microneedle (MN) patch and demonstrated that TCI using MN patches demonstrates high vaccination efficacy without adverse events in humans. In this study, we investigated the immune induction mechanism of TCI using our MN patch, focusing on inflammatory responses in the skin and on the dynamics, activation, and differentiation of various immunocompetent cells in draining lymph nodes (dLNs). We demonstrate that inflammatory cytokines such as IL-6 and TNF-α increased in the skin at an early stage after MN patch application, inducing the infiltration of macrophages and neutrophils and promoting the activation and migration of skin-resident antigen-presenting cells (Langerhans and Langerin^- dermal dendritic cells) to dLNs. Moreover, the activated antigen-presenting cells reaching the dLNs enhanced the differentiation of T (T_eff, T_em, and T_cm) and B (plasma and memory) cells. This may contribute to the efficient antigen-specific antibody production induced by TCI using MN patches. We believe that our findings reveal a part of the immune induction mechanism by TCI and provide useful information for the development and improvement of TCI formulations based on the immune induction mechanism.

Keywords: Antigen-presenting cell; Immune induction mechanism; Microneedle; Transcutaneous immunization.

MeSH terms

Administration, Cutaneous
Animals
Drug Delivery Systems
Immunization
Mice
Skin*
Vaccination*