Profiles of neutralizing antibody response in chronically human immunodeficiency virus type 1 clade B′-infected former plasma donors from China naive to antiretroviral therapy

Profiles of neutralizing antibody response in chronically human immunodeficiency virus type 1 clade B′-infected former plasma donors from China naive to antiretroviral therapy
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DOI:
10.1099/vir.0.043802-0
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发表时间:
2012-10-01
影响因子:
3.8
通讯作者:
Shao, Yiming
Shao, Yiming
中科院分区:
医学3区
文献类型:
--
作者:
Hu, Xintao;Hong, Kunxue;Shao, Yiming

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广泛中和抗体(NAb),如在慢性人类免疫缺陷病毒1型(HIV-1)感染中产生的抗体,被认为是有效HIV-1疫苗的关键成分。在此,我们使用一组25种Env假型病毒(包括进化枝B、C、A、CRF 07_BC和CRF 01_AE毒株),针对来自中国中部前血浆供体队列的103名受试者的血浆样本测量了NA B应答,这些受试者感染HIV-1进化枝B'至少10年,并且在采样时未接受过抗逆转录病毒治疗。我们发现,64%的样本(n=66)中和了至少一半的测试病毒,2%(n=2)中和了所有病毒,而5%(n=5)没有中和任何测试病毒。引人注目的是,29%的血浆样品(n=30)中和了>80%的测试病毒株,表明这些患者中存在广泛反应性NAb。当评估中和幅度(几何平均值1050滴度,GMT)或中和宽度与CD 4计数或血浆病毒载量的相关性时,仅观察到病毒载量与中和幅度(r=0.2189,P=0.0263)和病毒载量与中和宽度(r=0.1970,P=0.0461)之间存在显著正相关性。进展者和长期非进展者之间在广度(P=0.0316)和效力(P=0.0300)方面均观察到中度差异。进化枝内和进化枝间的GMT差异显著(P
Broadly neutralizing antibodies (NAbs) such as those generated in chronic human immunodeficiency virus type 1 (HIV-1) infection are considered a key component for an effective HIV-1 vaccine. Here, we measured NAb responses using a panel of 25 Env-pseudotyped viruses, including clade B, C, A, CRF07_BC and CRF01_AE strains, against plasma samples from 103 subjects in a former plasma donor cohort in central China, who were infected with HIV-1 clade B' for at least 10 years and naive to antiretroviral therapy at the time of sampling. We found that 64 % of samples (n=66) neutralized at least half of the viruses tested and 2% (n=2) neutralized all of the viruses, while 5% (n=5) neutralized none of the viruses tested. Strikingly, 29% of plasma samples (n=30) neutralized >80% of the viral strains tested, indicating the presence of broadly reactive NAbs in these patients. When the magnitude (geometric mean 1050 titres, GMTs) or breadth of neutralization was assessed for correlation with CD4 count or plasma viral load, the only significant positive correlations were observed between viral load and neutralization magnitude (r=0.2189, P=0.0263) and between viral load and neutralization breadth (r=0.1970, P=0.0461). A moderate difference between progressors and long-term non-progressors was observed in both the breadth (P=0.0316) and the potency (P=0.0300). A significant difference was found in the GMTs between intra-clade and inter-clade strains (P