PLoS Pathog：羊驼体内特殊抗体或可杀灭HIV

  大多数的疫苗都是通过诱导机体免疫反应产生中和性抗体抵御单一病原体来发挥作用的，而目前为止科学界尚未开发出抵御HIV的疫苗，然而研究者们一直在进行努力开发，近日，一项发表于国际杂志PLoS Pathogen上的研究论文中，来自伦敦大学的研究人员报道的一种来自羊驼机体抗体的组合或许可以中和一系列循环中的HIV。
  在HIV候选疫苗首次注射失败后，研究人员一直在努力寻找机体中可以产生特殊抗体的HIV感染个体，而当前的挑战就是寻找安全有效的疫苗成分来诱导机体产生中和性抗体，进而识别HIV并且阻断HIV及其亚型病毒的感染。
  文章中，研究人员Laura McCoy及其同事在羊驼机体中检测了特殊的免疫学步骤以及随之而来的免疫反应，此前研究人员发现一种特殊羊驼机体的抗体可以中和HIV，基于这些发现，研究人员随后又对另外两只羊驼进行免疫，并且鉴别出了三种新型中和性抗体的组合，而第四种HIV中和性羊驼抗体可以靶向作用HIV的CD4结合位点的不同部位，当使用抗体联合疗法时，研究者发现其可以中和所有60种不同的HIV菌株。
  为了理解为何对羊驼进行免疫就可以达到产生特殊组合型抗体的目的，研究人员在对羊驼进行第一轮及后续四轮疫苗注射后，收集其血细胞，对血细胞中抗体编码的基因进行测序分析，研究结果显示，中和性抗体并不是羊驼机体预先免疫所产生的，而其产生是由于免疫细胞重复接触到疫苗并且通过特殊抗体成熟所产生的反应而生成的。
  如今鼓舞人心的是在羊驼机体中发现了可以中和HIV的抗体，但抗体的水平却较低，而且经常并不能开发出保护性的疫苗，尽管如此，研究人员仍表示羊驼模型可以帮助研究人员检测四种广谱中和性抗体的生成，以及其是否可以达到组合杀灭HIV的目的。（转化医学网360zhyx.com）
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转化医学网推荐的原文摘要：

Molecular Evolution of Broadly Neutralizing Llama Antibodies to the CD4-Binding Site of HIV-1
PLoS Pathogens doi:10.1371/journal.ppat.1004552
Laura E. Mccoy, Lucy Rutten, Dan Frampton, Ian Anderson, Luke Granger, Rachael Bashford-Rogers, Gillian Dekkers, Nika M. Strokappe, Michael S. Seaman, Willie Koh, Vanina Grippo, Alexander Kliche, Theo Verrips, [ .. ], Robin A. Weiss
To date, no immunization of humans or animals has elicited broadly neutralizing sera able to prevent HIV-1 transmission; however, elicitation of broad and potent heavy chain only antibodies (HCAb) has previously been reported in llamas. In this study, the anti-HIV immune responses in immunized llamas were studied via deep sequencing analysis using broadly neutralizing monoclonal HCAbs as a guides. Distinct neutralizing antibody lineages were identified in each animal, including two defined by novel antibodies (as variable regions called VHH) identified by robotic screening of over 6000 clones. The combined application of five VHH against viruses from clades A, B, C and CRF_AG resulted in neutralization as potent as any of the VHH individually and a predicted 100% coverage with a median IC50 of 0.17 µg/ml for the panel of 60 viruses tested. Molecular analysis of the VHH repertoires of two sets of immunized animals showed that each neutralizing lineage was only observed following immunization, demonstrating that they were elicited de novo. Our results show that immunization can induce potent and broadly neutralizing antibodies in llamas with features similar to human antibodies and provide a framework to analyze the effectiveness of immunization protocols.