title: Enhancement of DNA vaccine potency against herpes simplex virus 1 by co-administration of an interleukin-18 expression plasmid as a genetic adjuvant.
abstract: In this study, the immune-modulatory and vaccine effects of using an interleukin (IL)-18 expression plasmid as a genetic adjuvant to enhance DNA vaccine-induced immune responses were investigated in a mouse herpes simplex virus 1 (HSV-1) challenge model. BALB/c mice were immunized by three intramuscular inoculations of HSV-1 glycoprotein D (gD) DNA vaccine alone or in combination with a plasmid expressing mature IL-18 peptide. Both the serum IgG2a/IgG1 ratio and T helper 1-type (Th1) cytokines [IL-2 and interferon (IFN)-gamma] were increased significantly by the co-injection of the IL-18 plasmid compared with the injection of gD DNA alone. However, the production of IL-10 was inhibited by IL-18 plasmid co-injection. Furthermore, IL-18 plasmid co-injection efficiently enhanced antigen-specific lymphocyte proliferation and the delayed-type hypersensitivity response. When mice were challenged with HSV-1 at the cornea, co-injection of IL-18 plasmid with gD DNA vaccine showed significantly better protection, manifested as lower corneal lesion scores and faster recovery. These experiments indicate that co-injection of an IL-18 plasmid with gD DNA vaccine efficiently induces Th1-dominant immune responses and improves the protective effect against HSV-1 infection.
authors.affiliation: Department of Biophysics, Institute of Basic Medical Sciences1 and Department of Ophthalmology, Peking Union Hospital3, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, PR China 2Department of Pharmacology, Beijing Institute of Ophthalmology, Beijing 100062, PR China.
authors.forename: Mingzhao
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Biophysics, Institute of Basic Medical Sciences1 and Department of Ophthalmology, Peking Union Hospital3, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, PR China 2Department of Pharmacology, Beijing Institute of Ophthalmology, Beijing 100062, PR China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Biophysics, Institute of Basic Medical Sciences1 and Department of Ophthalmology, Peking Union Hospital3, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, PR China 2Department of Pharmacology, Beijing Institute of Ophthalmology, Beijing 100062, PR China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Biophysics, Institute of Basic Medical Sciences1 and Department of Ophthalmology, Peking Union Hospital3, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, PR China 2Department of Pharmacology, Beijing Institute of Ophthalmology, Beijing 100062, PR China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Biophysics, Institute of Basic Medical Sciences1 and Department of Ophthalmology, Peking Union Hospital3, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, PR China 2Department of Pharmacology, Beijing Institute of Ophthalmology, Beijing 100062, PR China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Biophysics, Institute of Basic Medical Sciences1 and Department of Ophthalmology, Peking Union Hospital3, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, PR China 2Department of Pharmacology, Beijing Institute of Ophthalmology, Beijing 100062, PR China.
authors.forename: Fangtian
authors.initials: F
authors.lastname: Dong
authors.affiliation: Department of Biophysics, Institute of Basic Medical Sciences1 and Department of Ophthalmology, Peking Union Hospital3, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, PR China 2Department of Pharmacology, Beijing Institute of Ophthalmology, Beijing 100062, PR China.
authors.forename: Baoling
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Biophysics, Institute of Basic Medical Sciences1 and Department of Ophthalmology, Peking Union Hospital3, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, PR China 2Department of Pharmacology, Beijing Institute of Ophthalmology, Beijing 100062, PR China.
authors.forename: Guoxing
authors.initials: G
authors.lastname: Song
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D003315:Cornea / Q000276:immunology / Q000473:pathology / Q000821:virology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006561:Herpes Simplex / Q000276:immunology* / Q000517:prevention & control; D018259:Herpesvirus 1, Human / Q000276:immunology*; D006968:Hypersensitivity, Delayed; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D016207:Cytokines; D020382:Interleukin-18; D019444:Vaccines, DNA