南非金山大学(Wits University)研究人员描述了在两名感染上HIV的南非女性身上发现的HIV病毒外壳上的一种独特变化如何能够让她们制造出强大的抗体,其中这些抗体能够杀死全世界高达88%的HIV类型。这项突破性发现有助于人们开发出一种艾滋病疫苗。

-2012年11月《自然-医学》

中文翻译


【题目】一种HIV聚糖依赖的中和抗体表位通过免疫逃逸的进化

【译文】中和抗体有可能在一种保护性HIV-1疫苗中发挥重要作用。尽管通过接种诱导广泛地交叉中和(BCN)抗体的努力尚未成功,但少数个体在感染多年后可自然地产生抗体。然而,这样的抗体出现,以及病毒发展在形成这些反应中的作用尚不清楚。本研究表明,在靶向gp120外膜Asn332上的聚糖产生BCN抗体的两个HIV-1感染个体中,这种聚糖在初始感染病毒中缺乏。然而,通过免疫逃逸导致聚糖转移至332位的早期菌株特异性抗体,这种BCN表位在6个月内进化。 这两个缺乏332位氨基酸聚糖的病毒均对Asn332依赖的BCN单克隆抗体PGT128耐受,而获得这种聚糖的逃脱的突变体对该抗体敏感。对大序列和中和数据的分析表明与慢性病毒相比,332聚糖在转移的C亚型病毒中未被充分代表,慢性病毒中这种聚糖的缺失符合对PGT128的耐受。这些发现阐明了在驱动保守的BCN抗体表位进化中的早期抗体和病毒逃逸间的动态相互作用。

英文原稿


[Title]: Evolution of an HIV glycan–dependent broadly neutralizing antibody epitope through immune escape

 [Authors]:Penny L Moore,1, 2 Elin S Gray,1 C Kurt Wibmer,1, 2 Jinal N Bhiman,1, 2 Molati Nonyane,1 Daniel J Sheward,3 Tandile Hermanus,1 Shringkhala Bajimaya,4 Nancy L Tumba,1 Melissa-Rose Abrahams,3 Bronwen E Lambson,1 Nthabeleng Ranchobe,1 Lihua Ping,5 Nobubelo Ngandu,3 Quarraisha Abdool Karim,6 Salim S Abdool Karim,6 Ronald I Swanstrom,5 Michael S Seaman,4 Carolyn Williamson3 & Lynn Morris1, 2

[Abstract]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, whereas escaped variants that acquired this glycan were sensitive. Analysis of large sequence and neutralization data sets showed the 332 glycan to be significantly under-represented 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.

原文地址

http://www.nature.com/nm/journal/v18/n11/abs/nm.2985.html

留言


6 − 四 =


沪ICP备12028140号
点击这里给我发消息   点击这里给我发消息