title: Immunostimulant adjuvant patch enhances humoral and cellular immune responses to DNA immunization.
abstract: The focus of this report is on the development of an improved DNA immunization protocol, which takes advantage of the strengths of DNA immunization, as well as those associated with adjuvant delivered by transcutaneous immunostimulatory (IS) patches. Because transcutaneous delivery of adjuvants to the skin at the vaccination site has been shown to amplify the immune response to protein antigens, we hypothesized that the same IS patch when placed on the skin at the site of DNA injection could further enhance the immune response to a DNA influenza vaccine. We have combined an influenza DNA vaccine, hemagglutinin fused with three copies of complement C3d, to enhance uptake and antigen presentation, with an IS patch containing heat-labile enterotoxin from Escherichia coli. Coadministration of a potent adjuvant in IS patches placed on the skin at the site of DNA vaccination dramatically amplifies anti-influenza antibody immune response. Supplementing DNA vaccines with IS patches may be a particularly valuable strategy because DNA vaccines can be rapidly modified in response to mutations in pathogens, and individuals with compromised immune systems such as transplant patients and the elderly will benefit from the enhanced antibody response induced by the IS patches.
authors.affiliation: Department of Immunology, The Institute for Molecular Medicine, Huntington Beach, California, USA.
authors.forename: Mikayel
authors.initials: M
authors.lastname: Mkrtichyan
authors.forename: Anahit
authors.initials: A
authors.lastname: Ghochikyan
authors.forename: Nina
authors.initials: N
authors.lastname: Movsesyan
authors.forename: Adrine
authors.initials: A
authors.lastname: Karapetyan
authors.forename: Gayane
authors.initials: G
authors.lastname: Begoyan
authors.forename: Jianmei
authors.initials: J
authors.lastname: Yu
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Glenn
authors.forename: Ted M
authors.initials: TM
authors.lastname: Ross
authors.forename: Michael G
authors.initials: MG
authors.lastname: Agadjanyan
authors.forename: David H
authors.initials: DH
authors.lastname: Cribbs
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D000917:Antibody Formation / Q000502:physiology; D000938:Antigen-Presenting Cells / Q000276:immunology; D019470:Biolistics; D049109:Cell Proliferation; D015933:Complement C3d / Q000276:immunology; D004247:DNA / Q000008:administration & dosage*; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D007111:Immunity, Cellular / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D012867:Skin / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage*
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D019444:Vaccines, DNA; D015933:Complement C3d; D004247:DNA