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Partial efficacy of a broadly neutralizing antibody against cell-associated SHIV infection
Science Translational Medicine ( IF 17.1 ) Pub Date : 2017-08-09 , DOI: 10.1126/scitranslmed.aaf1483
Matthew S. Parsons 1 , Sarah B. Lloyd 1 , Wen Shi Lee 1 , Anne B. Kristensen 1 , Thakshila Amarasena 1 , Rob J. Center 1, 2 , Brandon F. Keele 3 , Jeffrey D. Lifson 3 , Celia C. LaBranche 4 , David Montefiori 4 , Bruce D. Wines 2 , P. Mark Hogarth 2 , Kristine M. Swiderek 5 , Vanessa Venturi 6 , Miles P. Davenport 6 , Stephen J. Kent 1, 7, 8
Affiliation  

Broadly neutralizing antibodies (BnAbs) protect macaques from cell-free simian/human immunodeficiency virus (SHIV) challenge, but their efficacy against cell-associated SHIV is unclear. Virus in cell-associated format is highly infectious, present in transmission-competent bodily fluids, and potentially capable of evading antibody-mediated neutralization. The PGT121 BnAb, which recognizes an epitope consisting of the V3 loop and envelope glycans, mediates antibody-dependent cellular cytotoxicity and neutralization of cell-to-cell HIV-1 transmission. To evaluate whether a BnAb can prevent infection after cell-associated viral challenge, we infused pigtail macaques with PGT121 or an isotype control and challenged animals 1 hour later intravenously with SHIVSF162P3-infected splenocytes. All five controls had high viremia 1 week after challenge. Three of six PGT121-infused animals were completely protected, two of six animals had a 1-week delay in onset of high viremia, and one animal had a 7-week delay in onset of viremia. The infused antibody had decayed on average to 2.0 μg/ml by 1 week after infusion and was well below 1 μg/ml (range, <0.1 to 0.8 μg/ml) by 8 weeks. The animals with a 1-week delay before high viremia had relatively lower plasma concentrations of PGT121. Transfer of 22 million peripheral blood mononuclear cells (PBMCs) stored at weeks 1 to 4 from the animal with the 7-week delayed onset of viremia into uninfected macaques did not initiate infection. Our results show that HIV-1–specific neutralizing antibodies have partial efficacy against cell-associated virus exposure in macaques. We conclude that sustaining high concentrations of bioavailable BnAb is important for protecting against cell-associated virus.



中文翻译:

广泛中和抗体针对与细胞相关的SHIV感染的部分功效

广泛中和的抗体(BnAbs)保护猕猴免受无细胞猿猴/人类免疫缺陷病毒(SHIV)攻击,但是它们对细胞相关SHIV的功效尚不清楚。细胞相关形式的病毒具有高度传染性,存在于具有传播能力的体液中,并且有可能逃避抗体介导的中和作用。PGT121 BnAb识别由V3环和包膜聚糖组成的表位,介导抗体依赖性细胞的细胞毒性和细胞间HIV-1传播的中和。为了评估BnAb是否可以预防细胞相关病毒攻击后的感染,我们向猪尾猕猴注入PGT121或同种型对照,并在1小时后向其静脉注射SHIV SF162P3攻击动物感染的脾细胞。攻击后1周,所有五个对照均具有高病毒血症。六只输注PGT121的动物中有三只受到完全保护,六只动物中的两只有高毒血症发作延迟1周的时间,而另一只动物有7周的病毒血症发作延迟的时间。输注后1周,注入的抗体平均衰减至2.0μg/ ml,并在8周后大大低于1μg/ ml(范围,<0.1至0.8μg/ ml)。高病毒血症发生前延迟1周的动物的PGT121血浆浓度相对较低。从第1周到第4周储存的2200万个外周血单核细胞(PBMC)从病毒中延迟了7周的病毒血症转移到未感染的猕猴中,这并未引发感染。我们的结果表明,HIV-1特异性中和抗体对猕猴中与细胞相关的病毒暴露具有部分功效。

更新日期:2017-08-10
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