GENE INOCULATION GENERATES IMMUNE-RESPONSES AGAINST HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1
GENE INOCULATION GENERATES IMMUNE-RESPONSES AGAINST HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1
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DOI：
10.1073/pnas.90.9.4156
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发表时间：
1993-05-01
影响因子：
11.1
通讯作者：
WEINER, DB
中科院分区：
文献类型：
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作者：
WANG, B;UGEN, KE;WEINER, DB
最近，已经开发出将DNA构建体直接引入哺乳动物体内组织的免疫技术。理论上，基因接种应该导致免疫宿主体内产生天然形式的抗原蛋白。在这里，我们介绍了使用这种技术给小鼠接种人类免疫缺陷病毒 1 型 (HIV-1) 包膜 DNA 构建体 (pM160)。小鼠肌肉注射 pM160，随后分析其抗 HIV 包膜免疫反应。从接种动物身上收集的抗血清在 ELISA 和免疫沉淀测定中与重组 HIV-1 包膜发生反应。该抗血清还含有能够中和 HIV-1 感染并在体外抑制 HIV-1 介导的合胞体形成的抗体。此外，来自接种 pM160 的动物的脾淋巴细胞表现出 HIV 包膜特异性增殖反应。基因接种技术模仿了减毒活病毒疫苗接种的特征，因此，最终可能被证明可用于快速开发安全有效的疫苗，因为它可以在不使用感染剂的情况下在体内产生相关抗原。
Recently, immunization techniques in which DNA constructs are introduced directly into mammalian tissue in vivo have been developed. In theory, gene inoculation should result in the production of antigenic proteins in a natural form in the immunized host. Here we present the use of such a technique for the inoculation of mice with a human immunodeficiency virus type 1 (HIV-1) envelope DNA construct (pM160). Mice were injected intramuscularly with pM160 and were subsequently analyzed for their anti-HIV envelope immune responses. Antisera collected from inoculated animals reacted with the recombinant HIV-1 envelope in ELISA and immunoprecipitation assays. The antisera also contained antibodies that were able to neutralize HIV-1 infection and inhibit HIV-1-mediated syncytium formation in vitro. Furthermore, splenic lymphocytes derived from pM160-inoculated animals demonstrated HIV-envelope-specific proliferative responses. The gene inoculation technique mimics features of vaccination with live attenuated viruses and, therefore, may ultimately prove useful in the rapid development of safe and efficacious vaccines as it provides for production of relevant antigen in vivo without the use of infectious agents.