Neutralization resistant HIV-1 primary isolates from antiretroviral naive chronically infected children in India
Neutralization resistant HIV-1 primary isolates from antiretroviral naive chronically infected children in India
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DOI：
10.1016/j.virol.2016.09.011
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发表时间：
2016-12-01
期刊：
影响因子：
3.7
通讯作者：
Luthra, Kalpana
中科院分区：
文献类型：
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作者：
Makhdoomi, Muzamil Ashraf;Singh, Deepti;Luthra, Kalpana
抗HIV-1广泛中和抗体（bnAb）已针对不同毒株的假病毒进行了广泛测试。我们产生和特点的HIV-1的主要分离株，抗逆转录病毒感染的印度儿童，并确定他们的易感性，已知的NAB。8株分离株均属于C亚型，嗜R5。这些病毒中的大多数对NAb的中和具有抗性，这表明已知可有效中和不同毒株的假病毒（成人和儿童）的bnAb对儿童原发分离株的有效性较低。有趣的是，AIIMS_329分离株显示出对PG 9和PG 16 bnAb中和的高敏感性，IC 50滴度为1.3和0.97 μ g/ml，表明该表位暴露于该病毒上。除AIIMS_506外，所有分离株均被同期血浆抗体中和。我们的研究结果表明，由于与自然感染中的病毒非常相似，因此应将原代分离株用于评估NAb作为儿童和成人有效的候选疫苗。(C)2016 Elsevier Inc. All rights reserved.
Anti-HIV-1 broadly neutralizing antibodies (bnAbs) have been extensively tested against pesudoviruses of diverse strains. We generated and characterized HIV-1 primary isolates from antiretroviral naive infected Indian children, and determined their susceptibility to known NAbs. All the 8 isolates belonged to subtype-C and were R5 tropic. Majority of these viruses were resistant to neutralization by NAbs, suggesting that the bnAbs, known to efficiently neutralize pseudoviruses (adult and pediatric) of different strains, are less effective against pediatric primary isolates. Interestingly, AIIMS_329 isolate displayed high susceptibility to neutralization by PG9 and PG16bnAbs, with IC50 titer of 1.3 and 0.97 mu g/ml, suggesting exposure of this epitope on this virus. All isolates except AIIMS_506 were neutralized by contemporaneous plasma antibodies. Our findings suggest that primary isolates, due to close resemblance to viruses in natural infection, should be used to evaluate NAbs as effective vaccine candidates in both children and adults. (C) 2016 Elsevier Inc. All rights reserved.