ADJUVANT-INDEPENDENT ENHANCED IMMUNE-RESPONSES TO RECOMBINANT HERPES-SIMPLEX VIRUS TYPE-1 GLYCOPROTEIN-D BY FUSION WITH BIOLOGICALLY-ACTIVE INTERLEUKIN-2

A truncated herpes simplex virus (HSV) type 1 glycoprotein D (t-gD) gene was fused to the human interleukin-2 (IL-2) gene (t-gD-IL-2 gene) and introduced into mouse myeloma Sp2/0 cells. The gene product, t-gD-IL-2, secreted from the cells was immunoprecipitated with five monoclonal antibodies specific for native gD. Purified t-gD-IL-2 supported the growth of IL-2-dependent cells, with a specific activity almost comparable to that of recombinant human IL-2. Mice immunized with t-gD-IL-2 in an adjuvant-freeform showed superior anti-HSV antibody responses, and were completely protected against HSV challenge, whereas immunization with t-gD adsorbed onto aluminium hydroxide (alum) partially failed to prevent the virus infection. The high immunogenicity of t-gD-IL-2 was due to the biological activity of the fused IL-2 rather than to a hapten-carrier effect of the IL-2 moiety, because mice primed with t-gD-IL-2 showed delayed-type hypersensitivity against stimulation with gD, but not against that with IL-2 antigen, and because a booster immunization with t-gD-IL-2 extensively augmented the response of anti-gD antibody, but not that of the anti-human IL-2 antibody. The serological half-life of IL-2 activity in mice injected with t-gD-IL-2 was prolonged to about four times that of rIL-2. However, when 1-gD-IL-2 was co-administered with human albumin (HSA), the mouse anti-HSA antibody response was slightly enhanced. Fused IL-2, therefore, influenced the immunological processing of the flanking t-gD rather than the non-specific activation of local immune responses. The receptor-mediated targeting effect of the IL-2 portion to antigen-presenting cells is discussed to account for the high immunogenicity of t-gD-IL-2.