在一项艾滋病病毒如何变异以应对免疫系统压力的研究中，美国埃默里大学疫苗中心研究人员得出的结论表明，艾滋病病毒能采取若干逃生路线，而不是以一个预定的路线来逃避免疫系统的压力，这意味着单一类型的中和抗体可能不足以遏制艾滋病病毒。此项研究结果发表在9月份的《公共科学图书馆·病原学》杂志上。

人体免疫系统具有压制早期艾滋病病毒的能力。最近的研究表明，大多数新感染患者都会发展出中和抗体。这些抗体是附着在病毒之上的水滴状血液蛋白，如果它们仅面对一个目标，它们就能允许患者作出自我防御。

但问题是，艾滋病病毒具有变异的能力，其掩饰自身的本领足以使其逃避抗体的压力，艾滋病病毒最终会瓦解免疫系统，使其耗竭。

埃默里大学研究团队的结果表明，即便研究人员能成功确定一种可刺激中和抗体的疫苗成分，艾滋病病毒快速变异的能力仍是一个令人讨厌的因子。埃默里大 学医学院病理学副教授辛西娅·德迪恩称，这些中和抗体的工作虽然非常出色，能够快速并努力地攻击艾滋病病毒，但艾滋病病毒总能想方设法逃脱。这说明，一个 单一类型的中和抗体可能不足以遏制艾滋病病毒。

德迪恩及其同事参加了由埃默里大学公共卫生学院全球卫生教授苏珊·艾伦领导的一项公共卫生计划，该计划在赞比亚招收了数千对其中一人呈艾滋病病毒阳性的异性夫妇，每3个月为其提供避孕套和相关咨询。尽管采取了这些措施，这些夫妇中仍有低水平的艾滋病病毒传播发生。

此次合作使研究团队可在感染发生后，两名参与者免疫系统持续作出反应的数周内即可得到患者的血样。相关研究人员分离出了艾滋病病毒感染的开始两年内 的单个病毒，并观察了患者自身的抗体是如何中和这些病毒的。结果表明，在极早期感染的患者中，中和抗体在数周之内即可出现，这比之前人们所认为的要早得 多。

在两名患者身上，某些病毒会使部分外层蛋白发生变异，变异后一种酶就有可能将一个糖分子附着其上，干扰抗体的攻击。但这种“聚糖盾牌”现象并不能在 所有病例中观察到。其他病毒则会使中和抗体直接粘连的部分外层蛋白发生变异。在两名患者中，病毒遗传代码中的许多变化对于其逃脱攻击来说都是必需的。

研究人员表示，如果想要搞清楚一个潜在的疫苗中应当有什么，他们就必须了解疫苗反应中的早期事件。此项研究证明，即使在一个患者身上，艾滋病病毒的 某些逃脱策略也正在进行中。这意味着，为了免受艾滋病病毒感染，某些患者可能需要准备多种中和抗体。了解这些病毒如何变异，将使研究人员能够在疫苗中选择 最佳的药物成分。

PLoS Pathog 5(9): e1000594. doi:10.1371/journal.ppat.1000594

Escape from Autologous Neutralizing Antibodies in Acute/Early Subtype C HIV-1 Infection Requires Multiple Pathways

Rong Rong1,2, Bing Li2, Rebecca M. Lynch1,2, Richard E. Haaland1,2¤, Megan K. Murphy1,2, Joseph Mulenga3,4, Susan A. Allen3,5, Abraham Pinter6,7, George M. Shaw8, Eric Hunter1,2, James E. Robinson9, S. Gnanakaran10, Cynthia A. Derdeyn1,2*

1 Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, United States of America, 2 Emory Vaccine Center at Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America, 3 Zambia Emory HIV Research Project, ZEHRP, Lusaka, Zambia, 4 Zambia Blood Transfusion Service, Lusaka, Zambia, 5 Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States of America, 6 Public Health Research Institute, Newark, New Jersey, United States of America, 7 New Jersey School of Medicine, University of Medicine and Dentistry, Newark, New Jersey, United States of America, 8 Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 9 Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana, United States of America, 10 Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America

One aim for an HIV vaccine is to elicit neutralizing antibodies (Nab) that can limit replication of genetically diverse viruses and prevent establishment of a new infection. Thus, identifying the strengths and weaknesses of Nab during the early stages of natural infection could prove useful in achieving this goal. Here we demonstrate that viral escape readily occurred despite the development of high titer autologous Nab in two subjects with acute/early subtype C infection. To provide a detailed portrayal of the escape pathways, Nab resistant variants identified at multiple time points were used to create a series of envelope (Env) glycoprotein chimeras and mutants within the background of a corresponding newly transmitted Env. In one subject, Nab escape was driven predominantly by changes in the region of gp120 that extends from the beginning of the V3 domain to the end of the V5 domain (V3V5). However, Nab escape pathways in this subject oscillated and at times required cooperation between V1V2 and the gp41 ectodomain. In the second subject, escape was driven by changes in V1V2. This V1V2-dependent escape pathway was retained over time, and its utility was reflected in the virus's ability to escape from two distinct monoclonal antibodies (Mabs) derived from this same patient via introduction of a single potential N-linked glycosylation site in V2. Spatial representation of the sequence changes in gp120 suggested that selective pressure acted upon the same regions of Env in these two subjects, even though the Env domains that drove escape were different. Together the findings argue that a single mutational pathway is not sufficient to confer escape in early subtype C HIV-1 infection, and support a model in which multiple strategies, including potential glycan shifts, direct alteration of an epitope sequence, and cooperative Env domain conformational masking, are used to evade neutralization.