Immune induction and modulation by topical ocular administration of plasmid DNA encoding antigens and cytokines.
In this article, the authors investigated if administration of eukaryotic expression plasmid DNA delivered to the ocular surface provided a means of inducing and modulating the immune response to herpes simplex virus (HSV). Topical application of gB DNA led to the development of HSV specific systemic humoral and cellular immunity. In addition, mucosal antibody was induced at both proximal and distal locations. Topically gB DNA immunized animals were protected against lethal challenge via either the systemic or the vaginal mucosal routes. Ocular pre-exposure to DNA encoding the cytokines interleukin (IL)-4 or IL-10, but not IL-2 or interferon-gamma, modulated the severity of the immunoinflammatory response to subsequent corneal infection with HSV. The present results indicate that the ocular surface provides a readily accessible site for DNA immunization and is suitable for both immune induction and modulation of the nature of the immune response that is induced.
Department of Microbiology, University of Tennessee, Knoxville 37996-0845, USA.
M
M
Daheshia
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N
Kuklin
E
E
Manickan
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S
Chun
B T
BT
Rouse
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000287:Administration, Topical; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D000956:Antigens, Viral / Q000235:genetics; D016207:Cytokines / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D005260:Female; D005815:Genetic Code; D018928:Immunity, Mucosal; D016849:Keratitis, Herpetic / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009883:Ophthalmic Solutions; D010957:Plasmids / Q000235:genetics*
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000956:Antigens, Viral; D016207:Cytokines; D009883:Ophthalmic Solutions; D004247:DNA