Transcutaneous Administration of Imiquimod Promotes T and B Cell Differentiation into Effector Cells or Plasma Cells.

Sachiko Hirobe,Ying-Shu Quan,Naoki Okada,Masashi Tachibana,Taki Yamasaki,Fumio Kamiyama,Sayami Ito

doi:10.3390/pharmaceutics14020385

Sachiko Hirobe, Ying-Shu Quan + Show 5 more

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https://doi.org/10.3390/pharmaceutics14020385

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Abstract

We are interested in promoting the development of transcutaneous immunization using microneedle technology and attempting to apply an adjuvant with transcutaneous immunization to improve the efficacy and reduce the amount of antigen and number of administrations needed. In this study, we collected basic information to help elucidate the mechanism responsible for the transcutaneous adjuvant activity of imiquimod (IMQ), which is a ligand of toll-like receptor (TLR) 7. In mouse groups administered ovalbumin (OVA), the OVA-specific IgG antibody titer of the IMQ-adjuvanted group was higher than that of the group administered OVA alone. No immune response bias due to transcutaneous IMQ administration was observed in terms of IgG1 (T helper cell [Th]2-type IgG subclass) and IgG2c (Th1-type IgG subclass) antibody titers. After the initial immunization, the IMQ-adjuvanted group showed increased migration of Langerhans cells to draining lymph nodes (dLNs) and active proliferation of OVA-specific CD4+ T cells. Transcutaneously administered IMQ did not affect the direction of CD4+ T cell differentiation, while promoted B cell activation and germinal center (GC) B cell differentiation. Immune staining revealed greater GC formation in the dLNs with the IMQ-adjuvanted group than in the OVA-alone group. In the secondary immune response, effector T cells increased in the dLNs and spleen, and effector memory T cells also increased in the spleen in the IMQ-adjuvanted group. In addition, our results suggested that the administration of IMQ enhanced B cell differentiation into plasma cells and GC B cells in the dLNs and spleen. In this study, we partially clarified the mechanism underlying the adjuvant activity of transcutaneously administered IMQ, which is required for the practical application of transcutaneous immunization with IMQ.

Highlights

Vaccines represent the only radical preventive measures against infectious diseases, and since the world’s first vaccination was developed by Jenner in 1796, humankind has overcome various infectious diseases by vaccination
The serum OVA-specific total IgG antibody titer increased slightly after the initial immunization when the mice were subjected to immunization with OVA alone, and the antibody titers increased with successive immunizations (Figure 1A)
The maximum applicable dose was used for screening purposes; it is plausible that proper adjuvant activity in transcutaneous immunity was not observed probably because of excessive immune response and cytotoxicity

Summary

Introduction

Vaccines represent the only radical preventive measures against infectious diseases, and since the world’s first vaccination (smallpox vaccine) was developed by Jenner in 1796, humankind has overcome various infectious diseases by vaccination. The latter two problems can prevent the spread of vaccination in developing countries and hinder the establishment of a rapid vaccine-supply system during the early stages of an epidemic, which is the most important period for controlling or preventing pandemics. The efficacy and safety of transcutaneous immunization using MN patches has already been demonstrated in animal experiments and clinical studies [1,2,3,4]. Based on these results, we are currently interested in applying transcutaneous immunization using

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