Chimeras between the human immunodeficiency virus (HIV-1) Env and vacciniavirus immunogenic proteins p14 and p39 generate in mice broadly reactive antibodies and specific activation of CD8+T cell responses to Env

A vaccine based on the envelope protein (Env) of the human immunodeficiency virus type 1 (HIV-1) that triggers widely reactive antibodies might be a d esirable approach to control virus infection. To expose epitopes which coul d induce broadly reactive antibodies against HIV-1 Env, we have generated v accinia virus (VV) recombinants that express Env fused at its N- or C-termi nus with two major antigenic proteins of VV, p14 (A27L gene) and p39 (A4L g ene). Biochemical analysis of the chimeric proteins in cell cultures reveal ed that, in all cases, recombinant viruses expressed the correct fusion pro teins. When p14 or p39 are fused at the N-terminus of Env the chimeric prot eins are poorly glycosylated but when p14 or p39 are fused at the C-terminu s of Env, the chimeric proteins are fully glycosylated. In Balb/c mice, imm unisation with the referred VV recombinants induced similar levels of (CD8 T cell specific responses to Env as immunisation with the entire Env prote in. The humoral immune response triggered by the fusion proteins was broade r than in animals immunised with VV expressing the entire Env (VVEnv1), and was directed to epitopes outside of the V3 loop (V1/V2, C1, C2, C4). One o f the chimeric constructs induced a better neutralising antibody response t han VVEnv1. We conclude that fusing VV proteins p14 or p39 to Env provides an effective means to induce broadly reactive antibodies and CD8+ T cell re sponses to Env. This approach might have utility against HIV and other path ogens. (C) 2000 Elsevier Science Ltd. All rights reserved.