Prospect for prevention of human immunodeficiency virus infection: purified 120-kDa envelope glycoprotein induces neutralizing antibody.

Prospect for prevention of human immunodeficiency virus infection: purified 120-kDa envelope glycoprotein induces neutralizing antibody.
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预防人类免疫缺陷病毒感染的前景:纯化的120-kDa包膜糖蛋白诱导中和抗体。

DOI:
10.1073/pnas.83.18.7023
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发表时间:
1986
影响因子:
11.1
通讯作者:
Fischinger,PJ
Fischinger,PJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Robey,WG;Arthur,LO;Matthews,TJ;Langlois,A;Copeland,TD;Lerche,NW;Oroszlan,S;Bolognesi,DP;Gilden,RV;Fischinger,PJ

文献摘要

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这项研究开启了开发一种安全的疫苗来对抗后天免疫缺陷综合征(AIDS)的努力,这种疾病是由一种被称为人类免疫缺陷病毒(HIV)的逆转录病毒(以前称为人类t细胞淋巴细胞病毒III型(HTLV-III))感染引起的。其他逆转录病毒模型显示纯化的外部糖蛋白亚基具有免疫原性。HIV外包膜糖蛋白(gp120)的分子大小为120 kDa,负责病毒的感染性,并在人体内引起强烈的抗体反应。纯化的HIV病毒制剂含有相对较少的gp120,因此使用HIV感染的细胞作为抗原源。gp120定位于细胞膜上,并与低水平的非离子洗涤剂溶解。糖蛋白进一步通过免疫亲和层析在从患者分离的igg制备的树脂上纯化。广泛透析和聚丙烯酰胺凝胶电泳后均质性达到。从感染细胞中分离的gp120与病毒粒子gp120的肽图显示结构相同,氨基末端氨基酸序列证实该分子是HIV基因组指定的。山羊、马和恒河猴(Macaca mulatta)的gp120免疫血清沉淀了同源抗原并中和了HIV的体外感染性。中和抗体的诱导表明gp120亚单位抗HIV疫苗在理论上是可能的。
This study initiates an effort to develop a safe vaccine against the acquired immunodeficiency syndrome (AIDS) that is caused by infection with a retrovirus designated human immunodeficiency virus (HIV) [formerly human T-cell lymphotropic virus type III (HTLV-III)]. Other retrovirus models have shown that purified external glycoprotein subunits are immunogenic. The external envelope glycoprotein of HIV (gp120) has a molecular size of 120 kDa, is responsible for virus infectivity, and induces strong antibody response in humans. Purified HIV virus preparations contain relatively little gp120 so HIV-infected cells were used as the antigen source. The gp120 was localized on cell membranes and was solubilized with low levels of nonionic detergent. The glycoprotein was further purified by immunoaffinity chromatography over a resin prepared from IgGs isolated from patients. Homogeneity was achieved following extensive dialysis and polyacrylamide gel electrophoresis. The gp120 isolated from infected cells was shown to be structurally identical by peptide maps to virion gp120 and the amino-terminal amino acid sequence confirmed that the molecule was specified by the HIV genome. Goat, horse, and rhesus monkey (Macaca mulatta) immune sera to gp120 precipitated the homologous antigen and neutralized the in vitro infectivity of HIV. The induction of neutralizing antibody indicates that a gp120 subunit vaccine against HIV is theoretically possible.