Failure of a human immunodeficiency virus (HIV) immune globulin to protect chimpanzees against experimental challenge with HIV.
Failure of a human immunodeficiency virus (HIV) immune globulin to protect chimpanzees against experimental challenge with HIV.
复制标题
人类免疫缺陷病毒（HIV）免疫球蛋白未能保护黑猩猩免受艾滋病毒的实验挑战。
DOI：
10.1073/pnas.85.18.6944
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发表时间：
1988
影响因子：
11.1
通讯作者：
Rey,F
中科院分区：
文献类型：
--
作者：
Prince,AM;Horowitz,B;Baker,L;Shulman,RW;Ralph,H;Valinsky,J;Cundell,A;Brotman,B;Boehle,W;Rey,F
为了评估针对人类免疫缺陷病毒（HIV）的被动免疫的可能功效，从HIV血清阳性供体的血浆制备免疫球蛋白，所述HIV血清阳性供体被选择为具有前12.5%的病毒中和抗体滴度的供体。用胃蛋白酶处理免疫球蛋白，使其静脉内耐受。我们称之为HIVIG的制剂在体外中和试验中以1：1000的平均稀释度中和100个组织培养50%感染剂量（TCID 50）的HIV。在制备过程中，HIVIG经过病毒灭活和去除程序，理论上可使HIV感染性降低10倍（25）。在9-10 ml/kg体重的剂量下，病毒灭活的源血浆和最终免疫球蛋白制剂在两只黑猩猩中均无感染性且无不良反应。静脉接种1 ml/kg HIVIG的两只黑猩猩和静脉接种10 ml/kg HIVIG的两只黑猩猩在1天后用400 TCID 50的体外中和试验中使用的相同HIV毒株（HTLV-IIIb）进行静脉攻击。所有动物都被感染了。在HIVIG接受者中病毒分离的潜伏期（通过与人单核细胞共培养）与接受正常抗HIV游离免疫球蛋白的对照动物中观察到的潜伏期没有显著差异。这些发现可能对理解实验性疫苗在黑猩猩实验中未能保护免受艾滋病毒攻击具有启示。
To assess the possible efficacy of passive immunization against human immunodeficiency virus (HIV) an immune globulin was prepared from plasma of HIV-seropositive donors selected to be among those having the top 12.5% of virus-neutralizing antibody titers. The immune globulin was treated with pepsin to render it intravenously tolerable. The preparation, which we termed HIVIG, neutralized 100 tissue culture 50% infective doses (TCID50) of HIV at an average dilution of 1:1000 in neutralization tests in vitro. During preparation HIVIG was subjected to virus inactivation and removal procedures that in theory resulted in a reduction in HIV infectivity by a factor of 10(25). At a dose of 9-10 ml/kg of body weight both the virus-inactivated source plasma and the final immunoglobulin preparation were noninfective and without adverse effect in two chimpanzees. Two chimpanzees inoculated intravenously with HIVIG at 1 ml/kg and two inoculated with 10 ml/kg were challenged intravenously 1 day later with 400 TCID50 of the same strain of HIV (HTLV-IIIb) used in neutralization assays in vitro. All animals became infected. Incubation periods to virus isolation (by cocultivation with human mononuclear cells) in HIVIG recipients did not differ significantly from the incubation period seen in a control animal that received a normal anti-HIV-free immunoglobulin. These findings may have implications for understanding the failure of experimental vaccines to protect against HIV challenge in chimpanzee experiments.