Effective ex vivo neutralization of human immunodeficiency virus type 1 in plasma by recombinant immunoglobulin molecules
Effective ex vivo neutralization of human immunodeficiency virus type 1 in plasma by recombinant immunoglobulin molecules
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DOI：
10.1128/jvi.70.4.2586-2592.1996
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发表时间：
1996-04-01
影响因子：
5.4
通讯作者：
Koup, RA
中科院分区：
文献类型：
--
作者：
Gauduin, MC;Allaway, GP;Koup, RA
我们检测了人单克隆抗体（免疫球蛋白G1 b12 [IgG 1b 12]和19 b）和基于CD 4的分子（CD 4-IgG 2和可溶性CD 4 [sCD 4]）在体外中和试验中直接从血清阳性供体血浆中中和人类免疫缺陷病毒1型的能力。IgG 1b 12和CD 4-IgG 2，浓度为1至25 μ g/ml，被发现在降低大多数血浆样本中的HIV-1滴度方面是有效的。当扩增从血浆样品中回收的病毒以生产病毒储备液时，未观察到体外传代储备液对IgG 1b 12和CD 4-IgG 2的中和敏感性与直接在血浆中进行的离体中和敏感性之间存在相关性。这些差异可能是由于病毒体外传代一次后发生的中和敏感性变化，或者可能与血浆中存在补体或抗体有关。此外，血浆来源的和植物血凝素激活的外周血单核细胞来源的病毒上的粘附分子的表达差异可能涉及。这些研究表明，IgG 1b 12和CD 4-IgG 2在体外和离体中和试验中具有广泛和有效的中和活性，应考虑用作潜在的免疫预防剂或治疗剂。
We tested the ability of human monoclonal antibodies (immunoglobulin G1bl2 [IgG1b12] and 19b) and CD4-based molecules (CD4-IgG2 and soluble CD4 [sCD4]) to neutralize human immunodeficiency virus type 1 directly from the plasma of seropositive donors in an ex vivo neutralization assay. IgG1b12 and CD4-IgG2, at concentrations from 1 to 25 mu g/ml, were found to be effective at reducing the HIV-1 titer in most plasma samples. When viruses recovered from plasma samples were expanded to produce virus stocks, no correlation between the neutralization sensitivities to IgG1b12 and CD4-IgG2 of the in vitro passaged stocks and those of the ex vivo neutralizations performed directly the plasma was observed. These differences could be due to changes in neutralization sensitivity that occur after one passage of the virus in vitro, or they could be related to the presence of complement or antibodies in the plasma. Furthermore, differences in expression of adhesion molecules on plasma-derived and phytohemagglutinin-activated peripheral blood mononuclear cell derived viruses could be involved. These studies suggest that IgG1b12 and CD4-IgG2 have broad and potent neutralizing activity in both in vitro and ex vivo neutralization assays and should be considered for use as potential immunoprophylactic or therapeutic agents.