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Co-Delivery of M2e Virus-Like Particles with Influenza Split Vaccine to the Skin Using Microneedles Enhances the Efficacy of Cross Protection

Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA
Komipharm Co., Ltd., Siheung, Gyeonggi-do 15094, Korea
School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
Animal and Plant Quarantine Agency, Gimcheon, Gyeongsangbukdo 39660, Korea
Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB T6G 2M9, Canada
Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceutics 2019, 11(4), 188;
Received: 20 March 2019 / Revised: 10 April 2019 / Accepted: 15 April 2019 / Published: 18 April 2019
(This article belongs to the Special Issue Drug Delivery Systems Using Various Microneedle Technologies)
PDF [2182 KB, uploaded 18 April 2019]


It is a high priority to develop a simple and effective delivery method for a cross-protective influenza vaccine. We investigated skin immunization by microneedle (MN) patch with human influenza split vaccine and virus-like particles containing heterologous M2 extracellular (M2e) domains (M2e5x virus-like particles (VLP)) as a cross-protective influenza vaccine candidate. Co-delivery of influenza split vaccine and M2e5x VLP to the skin by MN patch was found to confer effective protection against heterosubtypic influenza virus by preventing weight loss and reducing lung viral loads. Compared to intramuscular immunization, MN-based delivery of combined split vaccine and M2e5x VLPs shaped cellular immune responses toward T helper type 1 responses increasing IgG2a isotype antibodies as well as IFN-γ producing cells in mucosal and systemic sites. This study provides evidence that potential immunological and logistic benefits of M2e5x VLP with human influenza split vaccine delivered by MN patch can be used to develop an easy-to-administer cross-protective influenza vaccine. View Full-Text
Keywords: microneedle patch delivery; skin; cross protection; M2e; supplemented vaccines microneedle patch delivery; skin; cross protection; M2e; supplemented vaccines

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Kim, M.-C.; Kim, K.-H.; Lee, J.W.; Lee, Y.-N.; Choi, H.-J.; Jung, Y.-J.; Kim, Y.-J.; Compans, R.W.; Prausnitz, M.R.; Kang, S.-M. Co-Delivery of M2e Virus-Like Particles with Influenza Split Vaccine to the Skin Using Microneedles Enhances the Efficacy of Cross Protection. Pharmaceutics 2019, 11, 188.

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