VACCINATION WITH RECOMBINANT VACCINIA VIRUSES EXPRESSING ICP27 INDUCES PROTECTIVE IMMUNITY AGAINST HERPES-SIMPLEX VIRUS THROUGH CD4(+) TH1(+) T-CELLS

study was designed to evaluate the efficacy and mechanisms of protection mediated by recombinant vaccinia viruses encoding immediate-early (IE) proteins of herpes simplex virus type 2 (HSV-2). Three mouse strains were immunized against the IE proteins ICP27, ICP0, and ICP4, and mice were challenged intracutaneously in the zosteriform model with HSV-2 strain MS, Protection was observed only following immunization with the ICP27 construct and then only in the BALB/c mouse strain, Protection in BALB/c mice was ablated by CD4(+) T-cell suppression but remained intact in animals depleted of CD8(+) T cells, Moreover, protection could be afforded to SCID nude recipients with CD4(+) but not CD8(+) T cells from ICP27-immunized mice, Only BALB/c mice developed a delayed-type hypersensitivity reaction to HSV-2, and in vitro measurements of humoral and cell-mediated immunity revealed response patterns to ICP27 and HSV that differed between protected BALB/c and unprotected mouse strains. Accordingly, BALB/c responses showed antigen-induced cytokine profiles dominated by type 1 cytokines, whereas C57BL/6 and C3H/HeN mice generated cytokine responses mainly of the type 2 variety, Our results may indicate that protection against zosterification is mainly mediated by CD4(+) T cells that express a type 1 cytokine profile and that protective vaccines against HSV which effectively induce such T-cell responses should be chosen,