title: Microneedle delivery of an M2e-TLR5 ligand fusion protein to skin confers broadly cross-protective influenza immunity.
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.
authors.affiliation: Department of Microbiology and Immunology, and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: bwang3@emory.edu.
authors.forename: Bao-Zhong
authors.initials: BZ
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology, and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Chemical Engineering, Texas Tech University, Lubbock, TX 79409, USA.
authors.forename: Harvinder S
authors.initials: HS
authors.lastname: Gill
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100094, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: He
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100094, China.
authors.forename: Changbo
authors.initials: C
authors.lastname: Ou
authors.affiliation: Department of Microbiology and Immunology, and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology, and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology, and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Microbiology and Immunology, and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Han
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Prausnitz
authors.affiliation: Department of Microbiology and Immunology, and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: rcompan@emory.edu.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Compans
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002460:Cell Line; D004285:Dogs; D005408:Flagellin / Q000008:administration & dosage* / Q000276:immunology; D007109:Immunity; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage*; D008024:Ligands; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008845:Microinjections; D009339:Needles; D009976:Orthomyxoviridae Infections / Q000097:blood / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000276:immunology; D051198:Toll-Like Receptor 5 / Q000737:chemistry / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000008:administration & dosage* / Q000276:immunology; D000086082:Viroporin Proteins
chemical_list: D005408:Flagellin; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D008024:Ligands; D011993:Recombinant Fusion Proteins; D051198:Toll-Like Receptor 5; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins
keywords: Cross-protection; Influenza M2e; Microneedle array; TLR5 ligand; Universal influenza vaccine