Schnell M J, Foley H D, Siler C A, McGettigan J P, Dietzschold B, Pomerantz R J
Center for Human Virology and Department of Biochemistry and Molecular Pharmacology, Dorrance H. Hamilton Laboratories, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3544-9. doi: 10.1073/pnas.97.7.3544.
Recombinant, replication-competent rabies virus (RV) vaccine strain-based vectors were developed expressing HIV type I (HIV-1) envelope glycoprotein (gp160) from both a laboratory-adapted (CXCR4-tropic) and a primary (dual-tropic) HIV-1 isolate. An additional transcription stop/start unit within the RV genome was used to express HIV-1 gp160 in addition to the other RV proteins. The HIV-1 gp160 protein was stably and functionally expressed, as indicated by fusion of human T cell lines after infection with the recombinant RVs. Inoculation of mice with the recombinant RVs expressing HIV-1 gp160 induced a strong humoral response directed against the HIV-1 envelope protein after a single boost with recombinant HIV-1 gp120 protein. Moreover, high neutralization titers up to 1:800 against HIV-1 could be detected in the mouse sera. These data indicate that a live recombinant RV, a rhabdovirus, expressing HIV-1 gp160 may serve as an effective vector for an HIV-1 vaccine.
基于重组、具有复制能力的狂犬病病毒(RV)疫苗株构建了载体,用于表达来自实验室适应株(趋化因子CXCR4)和原代分离株(双嗜性)的I型人类免疫缺陷病毒(HIV-1)包膜糖蛋白(gp160)。RV基因组内的一个额外转录终止/起始单元用于在表达其他RV蛋白的同时表达HIV-1 gp160。重组RV感染后人T细胞系的融合表明,HIV-1 gp160蛋白得到稳定且功能性表达。用表达HIV-1 gp160的重组RV接种小鼠,在用重组HIV-1 gp120蛋白单次加强免疫后,诱导出针对HIV-1包膜蛋白的强烈体液反应。此外,在小鼠血清中可检测到高达1:800的抗HIV-1高中和滴度。这些数据表明,表达HIV-1 gp160的重组活RV(一种弹状病毒)可作为HIV-1疫苗的有效载体。