GENETIC IMMUNIZATION AGAINST HERPES-SIMPLEX-VIRUS PROTECTION IS MEDIATED BY CD4(-LYMPHOCYTES() T)

Plasmid DNA encoding proteins represent a convenient novel approach to vaccination. We have investigated this ''genetic immunization'' appro ach as a means to protect against herpes simplex virus (HSV) infection using a mouse zosteriform model that mimics several aspects of reacti vated HSV infection of humans. After i.m. immunization with plasmid DN A-encoding glycoprotein B (gB), (pc-gB), 80% of BALB/c mice were compl etely protected and lesions were delayed in the remaining animals. Upo n pc-gB vaccination, the animals developed both gB- and HSV-specific I gG Ab response and the isotype examination revealed a predominance of IgG2a. These mice also have low levels (1/16) of HSV-neutralizing Abs. Immune splenocytes obtained from pc-gB-immunized mice, when restimula ted in vitro with HSV resulted in production of type 1 cytokines. Evid ence for CD8(+)-mediated cytotoxic T lymphocyte response was equivocal . Protection could be adoptively transferred to nude mice recipients b y CD4(+) T cells from pc-gB-immunized mice but not by CD8(+) T cells. Our results demonstrate that genetic immunization is a potent means of inducing protection against HSV and that the mechanism of immunity re sponsible for clearing virus from cutaneous sites is principally by CD 4(+) T cells. It is likely that these cells are Th1 cells because type 1 cytokines were the major cytokines detected upon in vitro Ag stimul ation.