在一名 HIV-1 感染者中发现两种不同克隆谱系的独特广泛中和抗体特异性：对疫苗设计的影响。
Two distinct broadly neutralizing antibody specificities of different clonal lineages in a single HIV-1-infected donor: implications for vaccine design.
机构信息
Duke Human Vaccine Institute, Durham, North Carolina, USA.
出版信息
J Virol. 2012 Apr;86(8):4688-92. doi: 10.1128/JVI.07163-11. Epub 2012 Feb 1.
Abstract
Plasma from a small subset of subjects chronically infected with HIV-1 shows remarkable magnitude and breadth of neutralizing activity. From one of these individuals (CH0219), we isolated two broadly neutralizing antibodies (bnAbs), CH01 and VRC-CH31, from two clonal lineages of memory B cells with distinct specificities (variable loop 1 and 2 [V1V2] conformational specificity and CD4-binding site specificity, respectively) that recapitulate 95% of CH0219 serum neutralization breadth. These data provide proof of concept for an HIV-1 vaccine that aims to elicit bnAbs of multiple specificities.
摘要
从一小部分慢性感染 HIV-1 的个体的血浆中可以观察到显著的中和活性幅度和广度。从其中一个个体（CH0219）中，我们从具有不同特异性的记忆 B 细胞的两个克隆谱系中分离出两种广泛中和抗体（bnAbs），CH01 和 VRC-CH31，分别具有可变环 1 和 2（V1V2）构象特异性和 CD4 结合位点特异性，分别 recapitulate 95%的 CH0219 血清中和广度。这些数据为旨在引发多种特异性 bnAbs 的 HIV-1 疫苗提供了概念验证。
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本文引用的文献
1
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J Virol. 2011 Nov;85(21):11502-19. doi: 10.1128/JVI.05363-11. Epub 2011 Aug 17.
2
Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing.结构和深度测序揭示 HIV-1 中和抗体的定向进化。
Science. 2011 Sep 16;333(6049):1593-602. doi: 10.1126/science.1207532. Epub 2011 Aug 11.
3
Analysis of a clonal lineage of HIV-1 envelope V2/V3 conformational epitope-specific broadly neutralizing antibodies and their inferred unmutated common ancestors.分析 HIV-1 包膜 V2/V3 构象表位特异性广谱中和抗体的克隆谱系及其推断的未突变共同祖先。
J Virol. 2011 Oct;85(19):9998-10009. doi: 10.1128/JVI.05045-11. Epub 2011 Jul 27.
4
Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding.序列和结构上与 CD4 结合模拟广泛而有效的 HIV 抗体的趋同。
Science. 2011 Sep 16;333(6049):1633-7. doi: 10.1126/science.1207227. Epub 2011 Jul 14.
5
Mechanism of neutralization by the broadly neutralizing HIV-1 monoclonal antibody VRC01.广谱中和 HIV-1 单克隆抗体 VRC01 的中和机制。
J Virol. 2011 Sep;85(17):8954-67. doi: 10.1128/JVI.00754-11. Epub 2011 Jun 29.
6
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J Virol. 2011 May;85(10):4828-40. doi: 10.1128/JVI.00198-11. Epub 2011 Mar 9.
7
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8
Polyreactivity increases the apparent affinity of anti-HIV antibodies by heteroligation.多反应性通过异连接增加抗 HIV 抗体的表观亲和力。
Nature. 2010 Sep 30;467(7315):591-5. doi: 10.1038/nature09385.
9
A limited number of antibody specificities mediate broad and potent serum neutralization in selected HIV-1 infected individuals.在一些 HIV-1 感染者中，有限数量的抗体特异性可介导广泛而有效的血清中和作用。
PLoS Pathog. 2010 Aug 5;6(8):e1001028. doi: 10.1371/journal.ppat.1001028.
10
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