title: Microneedle delivery of trivalent influenza vaccine to the skin induces long-term cross-protection.
abstract: A painless self-immunization method with effective and broad cross-protection is urgently needed to prevent infections against newly emerging influenza viruses. In this study, we investigated the cross-protection efficacy of trivalent influenza vaccine containing inactivated A/PR/8/34 (H1N1), A/Hong Kong/68 (H3N2) and B/Lee/40 after skin vaccination using microneedle patches coated with this vaccine. Microneedle vaccination of mice in the skin provided 100% protection against lethal challenges with heterologous pandemic strain influenza A/California/04/09, heterogeneous A/Philippines/2/82 and B/Victoria/287 viruses 8 months after boost immunization. Cross-reactive serum IgG antibody responses against heterologous influenza viruses A/California/04/09, A/Philippines/2/82 and B/Victoria/287 were induced at high levels. Hemagglutination inhibition titers were also maintained at high levels against these heterogeneous viruses. Microneedle vaccination induced substantial levels of cross-reactive IgG antibody responses in the lung and cellular immune responses, as well as cross-reactive antibody-secreting plasma cells in the spleen. Viral loads in the lung were significantly (p < 0.05) reduced. All mice survived after viral challenges. These results indicate that skin vaccination with trivalent vaccine using a microneedle array could provide protection against seasonal epidemic or new pandemic strain of influenza viruses.
authors.affiliation: a Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST) , Daejeon, Korea.
authors.forename: Yeu-Chun
authors.initials: YC
authors.lastname: Kim
authors.affiliation: b Department of Biomedical Science, Graduate School, Kyung Hee University , Seoul, Korea.
authors.forename: Su-Hwa
authors.initials: SH
authors.lastname: Lee
authors.affiliation: c Department of Medical Zoology, Kyung Hee University School of Medicine , Seoul, Korea.
authors.forename: Won-Hyung
authors.initials: WH
authors.lastname: Choi
authors.affiliation: d Department of Chemical and Materials Engineering, University of Alberta , Edmonton, Alberta, Canada.
authors.forename: Hyo-Jick
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: e Department of Biochemistry, Dongguk University College of Medicine , Gyeongju, Korea.
authors.forename: Tae-Won
authors.initials: TW
authors.lastname: Goo
authors.affiliation: f Department of Pathology, Kyung Hee University Medical Center , Seoul, Korea.
authors.forename: Ju-Hie
authors.initials: JH
authors.lastname: Lee
authors.affiliation: c Department of Medical Zoology, Kyung Hee University School of Medicine , Seoul, Korea.
authors.forename: Fu-Shi
authors.initials: FS
authors.lastname: Quan
mesh_terms: D000818:Animals; D005260:Female; D007074:Immunoglobulin G / Q000097:blood*; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage*; D007271:Injections, Intradermal; D008807:Mice, Inbred BALB C; D009339:Needles; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*
chemical_list: D007074:Immunoglobulin G; D007252:Influenza Vaccines
keywords: Influenza; microneedle; protection; trivalent vaccine