title: Mucosal application of plasmid-encoded IL-15 sustains a highly protective anti-Herpes simplex virus immunity.
abstract: In a DNA immunization against Herpes simplex virus (HSV), we examined the ability of plasmid-encoded interleukin-15 (pIL-15) to induce and maintain the mucosal B and T cell immune response. pIL-15 generated memory CD8(+) T cell responses that were threefold higher and mainly maintained in the spleen, but high levels of immunoglobulin A antibodies were induced and maintained long-term in the vaginal mucosa. Both of these enhanced components of the immune responses were recalled rapidly upon challenge with a lethal dose of HSV McKrae, affording protection in mice immunized with codelivery of pIL-15. Our results show for the first time that intranasal administration of pIL-15 along with plasmid-encoded glycoprotein B of HSV leads to enhancement of primary and memory CD8(+) T cell responses as well as humoral immune response. Therefore, a mucosal immunization strategy that incorporates a potent cytokine such as IL-15 as an adjuvant might induce protective mucosal immune responses that constitute the initial barrier at mucosal portals of pathogen entry.
authors.affiliation: Department of Microbiology, University of Tennessee, Knoxville, 37996, USA.
authors.forename: Felix N
authors.initials: FN
authors.lastname: Toka
authors.forename: Barry T
authors.initials: BT
authors.lastname: Rouse
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000235:genetics; D000281:Administration, Intranasal; D000818:Animals; D000917:Antibody Formation / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D006561:Herpes Simplex / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy*; D007111:Immunity, Cellular / Q000235:genetics / Q000276:immunology; D018928:Immunity, Mucosal / Q000276:immunology*; D007070:Immunoglobulin A / Q000276:immunology; D019409:Interleukin-15 / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000276:immunology* / Q000821:virology; D010957:Plasmids / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D018139:Simplexvirus / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D014621:Vagina / Q000276:immunology* / Q000821:virology
chemical_list: D000276:Adjuvants, Immunologic; D007070:Immunoglobulin A; D019409:Interleukin-15; D019444:Vaccines, DNA