title: Topical application of HIV DNA vaccine with cytokine-expression plasmids induces strong antigen-specific immune responses.
abstract: The topical application of DNA vaccine to the skin is a useful method of immunization because of its simplicity, painlessness and economy. But the immune responses that it elicits are relatively low. In this study, we administered human immunodeficiency virus type-1 (HIV-1) DNA vaccine with cytokine-expressing plasmids to the skin of mice by a new topical application technique involving prior elimination of keratinocytes using fast-acting adhesive. Our results revealed that the topical application of HIV-1 DNA vaccine induced high levels of both humoral and cell-mediated immune activity against HIV-1 envelope antigen. Co-administration of the DNA vaccine with cytokine expression plasmids of IL-12 and granulocyte-macrophage colony-stimulating factor (GM-CSF) by this new method raised the levels of both the HIV-specific cytotoxic T lymphocyte (CTL) response and delayed-type hypersensitivity (DTH) and facilitated the induction of substantial immune responses by DNA vaccine. Skin biopsy sections, thus, immunized showed significant increases of S-100 protein-positive dendritic cells (DCs). These results suggest that the topical application method described here is an efficient route of DNA vaccine administration and that the immune response may be induced by DNA plasmids taken in by DCs, Langerhans cells (LCs), or others such as antigen-presenting cells. This new topical application is likely to be of benefit in clinical use.
authors.affiliation: Department of Bacteriology, School of Medicine, Yokohama City University, 236-0004, Yokohama, Japan.
authors.forename: L J
authors.initials: LJ
authors.lastname: Liu
authors.forename: S
authors.initials: S
authors.lastname: Watabe
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.forename: K
authors.initials: K
authors.lastname: Hamajima
authors.forename: N
authors.initials: N
authors.lastname: Ishii
authors.forename: E
authors.initials: E
authors.lastname: Hagiwara
authors.forename: K
authors.initials: K
authors.lastname: Onari
authors.forename: K Q
authors.initials: KQ
authors.lastname: Xin
authors.forename: K
authors.initials: K
authors.lastname: Okuda
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000279:Administration, Cutaneous; D000818:Animals; D015415:Biomarkers; D001706:Biopsy; D003869:Dermabrasion; D004353:Drug Evaluation, Preclinical; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015694:Gene Products, rev / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D015483:HIV Antibodies / Q000096:biosynthesis*; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D019302:HIV Envelope Protein gp160 / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular; D018664:Interleukin-12 / Q000235:genetics*; D007801:Langerhans Cells / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics; D009418:S100 Proteins / Q000032:analysis; D012867:Skin / Q000276:immunology / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D054321:rev Gene Products, Human Immunodeficiency Virus
chemical_list: D016915:AIDS Vaccines; D015415:Biomarkers; D015694:Gene Products, rev; D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D009418:S100 Proteins; D019444:Vaccines, DNA; D054321:rev Gene Products, Human Immunodeficiency Virus; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor