Determination of a statistically valid neutralization titer in plasma that confers protection against simian-human immunodeficiency virus challenge following passive transfer of high-titered neutralizing antibodies
Determination of a statistically valid neutralization titer in plasma that confers protection against simian-human immunodeficiency virus challenge following passive transfer of high-titered neutralizing antibodies
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DOI：
10.1128/jvi.76.5.2123-2130.2002
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发表时间：
2002-03-01
影响因子：
5.4
通讯作者：
Martin, MA
中科院分区：
文献类型：
--
作者：
Nishimura, Y;Igarashi, T;Martin, MA
我们先前报道了针对人类免疫缺陷病毒1型（HIV-1）包膜的高滴度中和抗体可以阻断被动转移后两只猴子中猴免疫缺陷病毒（SIV）/HIV嵌合病毒（SHIV）感染的建立（R.柴田等人，5：204-210，1999）。在本研究中，向15只猪尾猕猴给予递增量的中和免疫球蛋白G（IgG），以获得血浆中统计学有效的保护性中和终点滴度。使用体外试验，测量完全中和的挑战SHIV，我们相关的病毒接种时，血浆中的中和抗体的滴度（范围从1：3到1：123）与建立感染的病毒攻击的动物。本实验中15只猴中有10只无病毒，这是由于通过DNA PCR（外周血单核细胞和淋巴结细胞）、RNA PCR（血浆）、病毒分离和将淋巴结细胞悬液（10（8）个细胞）加8 ml全血从受保护动物转移至未处理猕猴中进行监测，中和IgG给药的结果。血浆中中和抗体的滴度经计算可保护99%的病毒攻毒猴，为1：38。
We previously reported that high-titered neutralizing antibodies directed against the human immunodeficiency virus type 1 (HIV-1) envelope can block the establishment of a simian immunodeficiency virus (SIV)/HIV chimeric virus (SHIV) infection in two monkeys following passive transfer (R. Shibata et al., Nat. Med. 5:204-210, 1999). In the present study, increasing amounts of neutralizing immunoglobulin G (IgG) were administered to 15 pig-tailed macaques in order to obtain a statistically valid protective neutralization endpoint titer in plasma. Using an in vitro assay which measures complete neutralization of the challenge SHIV, we correlated the titers of neutralizing antibodies in plasma at the time of virus inoculation (which ranged from 1:3 to 1:123) with the establishment of infection in virus-challenged animals. Ten of 15 monkeys in the present experiment were virus free as a result of neutralizing IgG administration as monitored by DNA PCR (peripheral blood mononuclear cells and lymph node cells), RNA PCR (plasma), virus isolation, and the transfer of lymph node cell suspensions (10(8) cells) plus 8 ml of whole blood from protected animals to naive macaques. The titer of neutralizing antibodies in the plasma calculated to protect 99% of virus-challenged monkeys was 1:38.