Ibuki K, Funahashi S I, Yamamoto H, Nakamura M, Igarashi T, Miura T, Ido E, Hayami M, Shida H
Institute for Virus Research, Kyoto University, Japan.
J Gen Virol. 1997 Jan;78 ( Pt 1):147-52. doi: 10.1099/0022-1317-78-1-147.
To develop effective vaccines against infection with human T cell leukaemia virus type I (HTLV-I), we constructed a recombinant vaccinia virus (WR-SFB5env) synthesizing the HTLV-I envelope (Env) gp46 protein under the control of a strong promoter, termed the ATI hybrid promoter. WR-SFB5env expressed a large quantity of gp46. In cynomolgus monkeys (Macaca fascicularis) immunized with WR-SFB5env, anti-HTLV-I Env antibody, including neutralizing antibody, was induced and remained at a high level until 136 weeks (2-6 years) post-infection (p.i.). These immunized monkeys had HTLV-I Env-specific cytotoxic T lymphocyte activity. At 136 weeks p.i., the immunized monkeys were challenged with an HTLV-I-producing cynomolgus T lymphocyte cell line. Neither HTLV-I antigen nor HTLV-I proviruses were detected in peripheral blood mononuclear cells, lymph nodes or spleens of the WR-SFB5env-immunized monkeys, in contrast to non-immunized control monkeys. These results indicate that a single immunization with WR-SFB5env induced prolonged humoral and cellular immune responses to HTLV-I and protected the monkeys against virus challenge.
为研发针对人类I型T细胞白血病病毒(HTLV-I)感染的有效疫苗,我们构建了一种重组痘苗病毒(WR-SFB5env),该病毒在一个名为ATI杂交启动子的强启动子控制下合成HTLV-I包膜(Env)gp46蛋白。WR-SFB5env表达了大量的gp46。在用WR-SFB5env免疫的食蟹猴(食蟹猕猴)中,诱导产生了包括中和抗体在内的抗HTLV-I Env抗体,并且在感染后(p.i.)136周(2 - 6年)一直维持在高水平。这些免疫的猴子具有HTLV-I Env特异性细胞毒性T淋巴细胞活性。在感染后136周,用产生HTLV-I的食蟹猴T淋巴细胞系对免疫的猴子进行攻击。与未免疫的对照猴子相比,在WR-SFB5env免疫的猴子的外周血单核细胞、淋巴结或脾脏中均未检测到HTLV-I抗原或HTLV-I前病毒。这些结果表明,单次用WR-SFB5env免疫可诱导对HTLV-I的长期体液免疫和细胞免疫反应,并保护猴子免受病毒攻击。