Evolution of an HIV glycan-dependent broadly neutralizing antibody epitope through immune escape.
Evolution of an HIV glycan-dependent broadly neutralizing antibody epitope through immune escape.
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作者：
中和抗体可能在预防性HIV-1疫苗中发挥关键作用。虽然通过疫苗接种引发广泛交叉中和（BCN）抗体的努力一直不成功，但少数人在感染多年后自然产生这些抗体。这些抗体是如何产生的，以及病毒进化在形成这些反应中的作用，都是未知的。在这里，我们表明，在两个HIV-1感染的人谁开发BCN抗体靶向聚糖在Asn 332的gp 120包膜，这种聚糖是不存在的初始感染病毒。然而，这种BCN表位在6个月内进化，通过免疫逃逸早期菌株特异性抗体，导致聚糖转移到位置332。在氨基酸332处缺乏聚糖的两种病毒对Asn 332依赖性BCN单克隆抗体PGT 128具有抗性（参考文献），而获得这种聚糖的逃逸变体是敏感的。对大序列和中和数据集的分析显示，与慢性病毒相比，332聚糖在传播的C亚型病毒中的代表性显著不足，该聚糖的缺失对应于对PGT 128的耐药性。这些发现强调了早期抗体和病毒逃逸之间的动态相互作用，推动了保守的BCN抗体表位的进化。
Neutralizing antibodies are likely to play a crucial part in a preventative HIV-1 vaccine. Although efforts to elicit broadly cross-neutralizing (BCN) antibodies by vaccination have been unsuccessful, a minority of individuals naturally develop these antibodies after many years of infection. How such antibodies arise, and the role of viral evolution in shaping these responses, is unknown. Here we show, in two HIV-1–infected individuals who developed BCN antibodies targeting the glycan at Asn332 on the gp120 envelope, that this glycan was absent on the initial infecting virus. However, this BCN epitope evolved within 6 months, through immune escape from earlier strain-specific antibodies that resulted in a shift of a glycan to position 332. Both viruses that lacked the glycan at amino acid 332 were resistant to the Asn332-dependent BCN monoclonal antibody PGT128 (ref.), whereas escaped variants that acquired this glycan were sensitive. Analysis of large sequence and neutralization data sets showed the 332 glycan to be significantly underrepresented in transmitted subtype C viruses compared to chronic viruses, with the absence of this glycan corresponding with resistance to PGT128. These findings highlight the dynamic interplay between early antibodies and viral escape in driving the evolution of conserved BCN antibody epitopes.
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DOI：
10.1126/science.1213256
发表时间：
2011-11-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Pejchal R;Doores KJ;Walker LM;Khayat R;Huang PS;Wang SK;Stanfield RL;Julien JP;Ramos A;Crispin M;Depetris R;Katpally U;Marozsan A;Cupo A;Maloveste S;Liu Y;McBride R;Ito Y;Sanders RW;Ogohara C;Paulson JC;Feizi T;Scanlan CN;Wong CH;Moore JP;Olson WC;Ward AB;Poignard P;Schief WR;Burton DR;Wilson IA
通讯作者：
Wilson IA
影响因子：
82.9
作者：
Bunnik, Evelien M.;Euler, Zelda;Schuitemaker, Hanneke
通讯作者：
Schuitemaker, Hanneke
影响因子：
15.8
作者：
Gray ES;Meyers T;Gray G;Montefiori DC;Morris L
通讯作者：
Morris L
影响因子：
3.7
作者：
van Loggerenberg F;Mlisana K;Williamson C;Auld SC;Morris L;Gray CM;Abdool Karim Q;Grobler A;Barnabas N;Iriogbe I;Abdool Karim SS;CAPRISA 002 Acute Infection Study Team
通讯作者：
CAPRISA 002 Acute Infection Study Team
影响因子：
5.4
作者：
Abrahams, M. -R.;Anderson, J. A.;Williamson, C.
通讯作者：
Williamson, C.