Induction of Protective Immunity against Herpes Simplex Virus with DNA Encoding the Immediate Early Protein ICP 27

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Abstract
Using a mouse zosteriform model that mimics human herpes simplex virus (HSV) infection in several aspects, the effectiveness of plasmid DNA encoding the immediate early protein ICP 27 was evaluated as a vaccine. Animals were immunized intramuscularly twice with DNA, then either challenged with virus or killed, and the nature of the immune response induced was measured. After intramuscular injection with plasmid DNA encoding ICP 27 (pc-ICP 27), solid protection was evident in 70–80% of mice and the lesions were delayed in the remaining animals. Immune splenocytes obtained from pc-ICP 27 immune mice showed HSV-specific lymphoproliferation, MHC-class I restricted cytotoxic T-lymphocyte (CTL) activity, and type 1 cytokine production. These animals also exhibited delayed-type hypersensitivity (DTH) reactions. Adoptive transfer studies conducted on syngeneic nude mice revealed that those recipients of immune CD4+ T cells, but not CD8+ T cells, were protected from subsequent HSV-1 (strain 17) challenge. Thus pc-ICP 27 DNA immunization protected the mice principally by CD4+ T cells and it is likely that these cells were Th-1 type because only type 1 cytokines were detectable after in vitro antigen stimulation. Our results indicate the potential value of DNA encoding nonstructural viral proteins as vaccines against HSV.