title: Long-term protective immunity from an influenza virus-like particle vaccine administered with a microneedle patch.
abstract: Skin vaccination with influenza virus-like particles (VLPs) using microneedles has been shown to induce protection similar to or better than that induced by intramuscular immunization. In this study, we examined the long-term protective efficacy of influenza (H1N1 A/PR/8/34) VLPs after skin vaccination using microneedle patches coated with the vaccine. Microneedle vaccination of mice in the skin induced 100% protection against lethal challenge infection with influenza A/PR/8/34 virus 14 months after a single vaccine dose. Influenza virus-specific total IgG response and hemagglutination inhibition (HAI) titers were maintained at high levels for over 1 year after microneedle vaccination. Microneedle vaccination also induced substantial levels of lung IgG and IgA antibody responses, and antibody-secreting plasma cells from spleen and bone marrow, as well as conferring effective control of lung viral loads, resulting in complete protection 14 months after vaccination. These strong and long-lasting immune responses were enabled in part by stabilization of the vaccine by formulation with trehalose during microneedle patch fabrication. Administration of the stabilized vaccine using microneedles was especially effective at enabling strong recall responses measured 4 days after lethal virus challenge, including increased HAI and antibody-secreting cells in the spleen and reduced viral titer and inflammatory response in the lung. The results in this study indicate that skin vaccination with VLP vaccine using a microneedle patch provides long-term protection against influenza in mice.
authors.affiliation: Department of Medical Zoology, Kyung Hee University School of Medicine, Seoul, South Korea.
authors.forename: Fu-Shi
authors.initials: FS
authors.lastname: Quan
authors.forename: Yeu-Chun
authors.initials: YC
authors.lastname: Kim
authors.forename: Jae-Min
authors.initials: JM
authors.lastname: Song
authors.forename: Hye Suk
authors.initials: HS
authors.lastname: Hwang
authors.forename: Richard W
authors.initials: RW
authors.lastname: Compans
authors.forename: Mark R
authors.initials: MR
authors.lastname: Prausnitz
authors.forename: Sang-Moo
authors.initials: SM
authors.lastname: Kang
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002626:Chemistry, Pharmaceutical; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005260:Female; D006385:Hemagglutination Inhibition Tests; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D010950:Plasma Cells / Q000276:immunology; D013154:Spleen / Q000276:immunology; D016019:Survival Analysis; D014611:Vaccination / Q000379:methods*; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage* / Q000276:immunology*; D019562:Viral Load
chemical_list: D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D058425:Vaccines, Virus-Like Particle