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C-di-GMP with influenza vaccine showed enhanced and shifted immune responses in microneedle vaccination in the skin

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Abstract

A microneedle is a biomedical device which consists of multiple micron scale needles. It is widely used in various fields to deliver drugs and vaccines to the skin effectively. However, when considering improved vaccine efficacy in microneedle vaccination, it is important to find an appropriate adjuvant that is able to be used in transdermal delivery. Herein, we demonstrated the applicability of c-di-GMP, which is a stimulator of interferon genes (STING) agonist, as an adjuvant for influenza microneedle vaccination. Thus, 2 and 10 μg of GMP with the influenza vaccine were coated onto a microneedle, and then, BALB/c mice were immunized with the coated microneedle to investigate the immunogenicity and protection efficacy of the influenza microneedle vaccination. As a result, the adjuvant groups had an enhanced IgG response, IgG subtypes and HI titer compared to the vaccine only group. In addition to the humoral immunity, the use of an adjuvant has also been shown to improve the cellular immune response. In a challenge study, adjuvant groups had a 100% survival rate and rapid weight recovery. Taken together, this study confirms that GMP is an effective adjuvant for influenza microneedle vaccination.

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Acknowledgments

This work was financially supported by the Ministry of Science and ICT of Korea (NRF-2019R1A4A1024116, NRF-2019R1A2C2085962, and NRF-2018M3A9E2024583).

Ethics statement

All animal procedures conducted in this paper (permit number: KU16163) were reviewed, approved, and supervised by the Institutional Animal Care and Use Committee of Konkuk University.

Conflict of interest

All of authors do not have conflict of interest.

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  1. Ju-Hyung Shin and Ji-Ho Lee contributed equally to this work.

Authors and Affiliations

  1. Department of Chemical and Biomolecular engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea

    Ju-Hyung Shin, Seong Dong Jeong, Hyo Won Lee & Yeu-Chun Kim

  2. Avian Disease Laboratory, College of Veterinary Medicine, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul, Republic of Korea

    Ji-Ho Lee, Jin-Yong Noh & Chang-Seon Song

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Shin, JH., Lee, JH., Jeong, S.D. et al. C-di-GMP with influenza vaccine showed enhanced and shifted immune responses in microneedle vaccination in the skin. Drug Deliv. and Transl. Res. 10, 815–825 (2020). https://doi.org/10.1007/s13346-020-00728-1

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