title: Dose sparing enabled by skin immunization with influenza virus-like particle vaccine using microneedles.
abstract: To address the limitations of conventional influenza vaccine manufacturing and delivery, this study investigated administration of virus-like particle (VLP) influenza vaccine using a microneedle patch. The goal was to determine if skin immunization with influenza VLP vaccine using microneedles enables dose sparing. We found that low-dose influenza (A/PR/8/34 H1N1) VLP vaccination using microneedles was more immunogenic than low-dose intramuscular (IM) vaccination and similarly immunogenic as high-dose IM vaccination in a mouse model. With a 1μg dose of vaccine, both routes showed similar immune responses and protective efficacy, with microneedle vaccination being more effective in inducing recall antibody responses in lungs and antibody secreting cells in bone marrow. With a low dose of vaccine (0.3μg), microneedle vaccination induced significantly superior protective immunity, which included binding and functional antibodies as well as complete protection against a high dose lethal infection with A/PR/8/34 virus, whereas IM immunization provided only partial (40%) protection. Therefore, this study demonstrates that microneedle vaccination in the skin confers more effective protective immunity at a lower dose, thus providing vaccine dose-sparing effects.
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Fu-Shi
authors.initials: FS
authors.lastname: Quan
authors.forename: Yeu-Chun
authors.initials: YC
authors.lastname: Kim
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: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001853:Bone Marrow / Q000276:immunology / Q000821:virology; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004867:Equipment Design; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006387:Hemagglutination, Viral; D007074:Immunoglobulin G / Q000097:blood; D018836:Inflammation Mediators / Q000378:metabolism; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D008168:Lung / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008845:Microinjections; D008904:Miniaturization; D009339:Needles; D009500:Neutralization Tests; D012867:Skin / Q000276:immunology* / Q000821:virology; D013997:Time Factors; D022721:Vaccines, Virosome / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D007074:Immunoglobulin G; D018836:Inflammation Mediators; D007252:Influenza Vaccines; D022721:Vaccines, Virosome