Microneedle delivery of an M2e-TLR5 ligand fusion protein to skin confers broadly cross-protective influenza immunity

• Type of Material: Article
• Authors: Baozhong Wang, Emory University; Harvinder S. Gill, Emory University; Cheng He, China Agricultural University; Changbo Ou, China Agricultural University; Li Wang, Emory University; Ying-Chun wang, Emory University; Hao Feng, Emory University; Han Zhang, Emory University; Mark R. Prausnitz, Emory University; Richard W Compans, Emory University
• Language: English
• Date: 2014-03-28
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 Elsevier B.V.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jconrel.2014.01.002
• Title of Journal or Parent Work: Journal of Controlled Release
• ISSN: 0168-3659
• Volume: 178
• Issue: 1
• Start Page: 1
• End Page: 7
• Grant/Funding Information: This study was supported by the National Institute of Allergy and Infectious Diseases [R01AI101047 to BZW, R01AI068003 to RWC, and R01EB006369 to MRP].
• Keywords: VACCINE; MATRIX PROTEIN-2; M2-PROTEIN; FLAGELLIN; Microneedle array; Chemistry, Multidisciplinary; M2 PROTEIN; Universal influenza vaccine; TLR5 ligand; Science & Technology; Life Sciences & Biomedicine; Physical Sciences; Influenza M2e; IMMUNIZATION; ECTODOMAIN; MICE; DRUG; Chemistry; Pharmacology & Pharmacy; MONOCLONAL-ANTIBODY; Cross-protection
• Research Categories: Health Sciences, Immunology; Engineering, Biomedical

Abstract

Influenza vaccines with broad cross-protection are urgently needed to prevent an emerging influenza pandemic. A fusion protein of the Toll-like receptor (TLR) 5-agonist domains from flagellin and multiple repeats of the conserved extracellular domain of the influenza matrix protein 2 (M2e) was constructed, purified and evaluated as such a vaccine. A painless vaccination method suitable for possible self-administration using coated microneedle arrays was investigated for skin-targeted delivery of the fusion protein in a mouse model. The results demonstrate that microneedle immunization induced strong humoral as well as mucosal antibody responses and conferred complete protection against homo- and heterosubtypic lethal virus challenges. Protective efficacy with microneedles was found to be significantly better than that seen with conventional intramuscular injection, and comparable to that observed with intranasal immunization. Because of its advantages for administration, safety and storage, microneedle delivery of M2e-flagellin fusion protein is a promising approach for an easy-to-administer universal influenza vaccine.