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

• Type of Material: Article
• Authors: Min-Chui Kim, Georgia State University; Ki-Hye Kim, Georgia State University; Jeong Woo Lee, Georgia Institute of Technology; Yu-Na Lee, Georgia State University; Hyo-Jick Choi, University of Alberta; Yu-Jin Jung, Georgia State University; Yu-Jin Kim, Georgia State University; Richard W Compans, Emory University; Mark R. Prausnitz, Emory University; Sang-Moo Kang, Georgia State University
• Language: English
• Date: 2019-04-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2019 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/pharmaceutics11040188
• Title of Journal or Parent Work: Pharmaceutics
• ISSN: 1999-4923
• Volume: 11
• Issue: 4
• Grant/Funding Information: This work was supported by NIH/NIAID grants AI105170 (S.M.K.), AI093772 (S.M.K.) and AI1134132 (S.M.K.).
• Keywords: A VIRUS; DISSOLVING MICRONEEDLE; CONFER; cross protection; Science & Technology; BROAD; Life Sciences & Biomedicine; skin; CHALLENGES; HETEROSUBTYPIC IMMUNITY; supplemented vaccines; M2e; H1N1; SWINE; EXTRACELLULAR DOMAINS; T-CELLS; microneedle patch delivery; Pharmacology & Pharmacy
• Research Categories: Engineering, Biomedical; Biology, Virology; Chemistry, Pharmaceutical

Abstract

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.