INDUCTION OF PROTECTIVE IMMUNITY AGAINST HERPES-SIMPLEX VIRUS WITH DNA ENCODING THE IMMEDIATE-EARLY PROTEIN ICP-27

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 c hallenged with virus or killed, and the nature of the immune response induced was measured. After intramuscular injection with plasmid DNA e ncoding ICP 27 (pc-ICP 27), solid protection was evident in 70-80% of mice and the lesions were delayed in the remaining animals. Immune spl enocytes obtained from pc-ICP 27 immune mice showed HSV-specific lymph oproliferation, MHC-class I restricted cytotoxic T-lymphocyte (CTL) ac tivity, and type 1 cytokine production. These animals also exhibited d elayed-type hypersensitivity (DTH) reactions. Adoptive transfer studie s conducted on syngeneic nude mice revealed that those recipients of i mmune CD4(+) T cells, but not CD8(+) T cells, were protected from subs equent HSV-1 (strain 17) challenge. Thus pc-ICP 27 DNA immunization pr otected the mice principally by CD4(+) T cells and it is likely that t hese cells were Th-1 type because only type 1 cytokines were detectabl e after in vitro antigen stimulation. Our results indicate the potenti al value of DNA encoding nonstructural viral proteins as vaccines agai nst HSV.