title: Microneedle vaccination with stabilized recombinant influenza virus hemagglutinin induces improved protective immunity.
abstract: The emergence of the swine-origin 2009 influenza pandemic illustrates the need for improved vaccine production and delivery strategies. Skin-based immunization represents an attractive alternative to traditional hypodermic needle vaccination routes. Microneedles (MNs) can deliver vaccine to the epidermis and dermis, which are rich in antigen-presenting cells (APC) such as Langerhans cells and dermal dendritic cells. Previous studies using coated or dissolvable microneedles emphasized the use of inactivated influenza virus or virus-like particles as skin-based vaccines. However, most currently available influenza vaccines consist of solubilized viral protein antigens. Here we test the hypothesis that a recombinant subunit influenza vaccine can be delivered to the skin by coated microneedles and can induce protective immunity. We found that mice vaccinated via MN delivery with a stabilized recombinant trimeric soluble hemagglutinin (sHA) derived from A/Aichi/2/68 (H3) virus had significantly higher immune responses than did mice vaccinated with unmodified sHA. These mice were fully protected against a lethal challenge with influenza virus. Analysis of postchallenge lung titers showed that MN-immunized mice had completely cleared the virus from their lungs, in contrast to mice given the same vaccine by a standard subcutaneous route. In addition, we observed a higher ratio of antigen-specific Th1 cells in trimeric sHA-vaccinated mice and a greater mucosal antibody response. Our data therefore demonstrate the improved efficacy of a skin-based recombinant subunit influenza vaccine and emphasize the advantage of this route of vaccination for a protein subunit vaccine.
authors.affiliation: Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Weldon
authors.forename: Maria P
authors.initials: MP
authors.lastname: Martin
authors.forename: Vladimir
authors.initials: V
authors.lastname: Zarnitsyn
authors.forename: Baozhong
authors.initials: B
authors.lastname: Wang
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Koutsonanos
authors.forename: Ioanna
authors.initials: I
authors.lastname: Skountzou
authors.forename: Mark R
authors.initials: MR
authors.lastname: Prausnitz
authors.forename: Richard W
authors.initials: RW
authors.lastname: Compans
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage / Q000276:immunology*; D018928:Immunity, Mucosal; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007271:Injections, Intradermal / Q000379:methods; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D016019:Survival Analysis; D018417:Th1 Cells / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D019562:Viral Load
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic