重组狂犬病病毒作为潜在的HIV-1活病毒疫苗。
Recombinant rabies virus as potential live-viral vaccines for HIV-1.
作者信息
Schnell M J, Foley H D, Siler C A, McGettigan J P, Dietzschold B, Pomerantz R J
机构信息
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.
出版信息
Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3544-9. doi: 10.1073/pnas.97.7.3544.
Abstract
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.
摘要
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。
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