Nat Med:广泛中和抗体为HIV疫苗开发铺平道路

2016-10-15 佚名 生物谷

少量HIV感染者产生具有令人吃惊效应的抗体:这些抗体不仅抵抗这些人体内自身携带的HIV毒株,而且也抵抗在全世界传播的不同HIV亚型。如今,在一项新的研究中,来自瑞士苏黎世大学和苏黎世大学医院的研究人员揭示出哪些因素导致人体形成这些被称作广泛中和抗体(bnAbs)的抗体,因而为开发HIV疫苗开辟新的途径。相关研究结果近期发表在Nature Medicine期刊上,论文标题为“Determin


少量HIV感染者产生具有令人吃惊效应的抗体:这些抗体不仅抵抗这些人体内自身携带的HIV毒株,而且也抵抗在全世界传播的不同HIV亚型。如今,在一项新的研究中,来自瑞士苏黎世大学和苏黎世大学医院的研究人员揭示出哪些因素导致人体形成这些被称作广泛中和抗体(bnAbs)的抗体,因而为开发HIV疫苗开辟新的途径。相关研究结果近期发表在Nature Medicine期刊上,论文标题为“Determinants of HIV-1 broadly neutralizing antibody induction”。

从HIV研究中,我们知道大约1%的HIV感染者产生抵抗不同HIV毒株的抗体。这些bnAbs结合到HIV表面上很少发生变化且在不同HIV毒株中是相同的结构上。这些被称作“突起(spike)”的由糖和蛋白组成的复合体是唯一的来自HIV本身的而且能够被免疫系统通过抗体发动攻击的表面结构。由于这些抗体的广泛影响,它们成为开发有效地抵抗HIV的疫苗的基石。

病毒载量、病毒多样性和感染持续时间促进抗体产生

在这项新的研究中,研究人员对导致抵抗HIV的bnAbs产生的因素进行广泛研究。他们研究了瑞士HIV队列研究(Swiss HIV Cohort Study, SHCS)和苏黎世原发性HIV感染研究(Zurich Primary HIV Infection Study, ZPHIS)中记录的大约4500名HIV感染者,从中鉴定出239人能够产生这样的抗体。

首先,三种疾病特异性的特征是比较重要的:存在于体内的病毒数量,发现的病毒类型多样性以及未接受治疗的HIV感染持续时间。苏黎世大学医院临床传染病教授Huldrych Günthard解释道,“我们的研究能够让我们首次证实这三种特征---病毒载量、病毒多样性和感染持续时间---中的任何一种都会相互独立地影响bnAbs产生。因此,我们在设计HIV疫苗时不必考虑所有的这三种特征。考虑到疫苗接种的长期性,这是特别重要的---利用疫苗模拟一种更长的未接受治疗的HIV感染是不可能的。”

黑人更高频率地产生广泛中和抗体(bnAbs)

第二个因素涉及种族:黑人HIV感染者要比白人HIV感染者更加高频率地产生抵抗HIV的bnAbs---不论这项研究分析的其他因素。对苏黎世大学医院医学病毒学教授Alexandra Trkola而言,这一令人吃惊的发现需要接受更加密切的研究:“首先,我们需要更加精确地理解不同种族的人的遗传、地理和社会经济因素在产生这些抗体中起着多大的重要性和何种影响。”

不同的HIV亚型影响这些抗体的结合位点

第三个因素涉及HIV病毒亚型对抗体形成的影响。尽管抗体产生的频率仍然不受影响,但是研究人员发现HIV病毒亚型对形成的抗体类型产生较强的影响。HIV亚型B更可能导致靶向HIV病毒表面上结合到人免疫细胞上的一个区域,即CD4结合位点。相比之下,非亚型B的HIV偏好产生结合到HIV病毒突起(V2聚糖)的一个糖组分上的抗体。因此,依赖于HIV病毒亚型,HIV病毒衣壳上的特异性结构特征影响这些抗体的结合特异性。

Trkola作出结论,“我们的结果证实不同的因素如何促进广泛性抵抗不同HIV病毒毒株的抗体产生。这将为我们系统地推进有效地抵抗HIV的疫苗开发铺平道路。”

原始出处

Peter Rusert, Roger D Kouyos, Claus Kadelka, Hanna Ebner, Merle Schanz, Michael Huber, Dominique L Braun, Nathanael Hozé, Alexandra Scherrer, Carsten Magnus, Jacqueline Weber, Therese Uhr, Valentina Cippa, Christian W Thorball, Herbert Kuster, Matthias Cavassini, Enos Bernasconi, Matthias Hoffmann, Alexandra Calmy, Manuel Battegay, Andri Rauch, Sabine Yerly, Vincent Aubert, Thomas Klimkait, Jürg Böni, Jacques Fellay, Roland R Regoes, Huldrych F Günthard, Alexandra Trkola, The Swiss HIV Cohort Study.Determinants of HIV-1 broadly neutralizing antibody induction.Nat Med.2016



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    2016-12-09 liye789132251
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    2016-10-18 1e10c84am36(暂无匿称)

    文章很好,继续学习

    0

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  来自美国斯克里普斯研究所(TSRI)的科学家们发现,一个可广泛中和不同艾滋病毒株的抗体家族演变出了显著不同的结构来攻击病毒上的一个脆弱位点。研究结果为未来的HIV疫苗设计提供了一些新线索。相关论文在9月25日《细胞》(Cell)杂志上。   斯克里普斯研究所Skaggs化学生物学研究所成员、结构生物学教授 Ian Wilson 

盘点:2016年5月13日Science期刊精华

本周又有一期新的Science期刊(2016年5月13日)发布,它有哪些精彩研究呢?让小编一一道来。1. Science:一箭三雕!HIV新靶点助推更强疫苗开发在一项新的研究中,来自美国国家卫生研究院(NIH)等多家机构的研究人员取得三项突破。他们发现HIV的一个新的可被疫苗攻击的脆弱位点、一种结合这个靶位点的广泛中和抗体,以及这种抗体如何阻止这种病毒感染细胞。相关研究结果发表在2016年5月

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近日,刊登在国际杂志Nature Structural & Molecular Biology上的一篇研究报告中,来自杜克大学的研究者在HIV研究领域取得了突破性的成果,他们通过研究开发了一种的3D“设计师”蛋白,一旦将这种蛋白注射入HIV患者机体中,就会帮助患者机体免疫系统较好地制造抗体来抵御HIV的侵袭。目前全球超过3500万人感染HIV,而且每年都会有200万人死亡AIDS;一旦个体

JAMA:HIV疫苗开发或需另辟蹊径

开发抑制HIV感染的有效疫苗是终结HIV/AIDS流行的关键一步,然而截止到目前为止, 2009年在泰国进行的大型临床试验表明仅RV144疫苗或许是最为有效的HIV疫苗,该疫苗可以帮助降低31%的HIV感染率,如今研究者们可以通过研究来改善RV144的效率,同时研究者们还希望通过努力开发出更多新型疫苗来诱导更广泛的中和性抗体来阻断一系列HIV突变体引发的感染。 然而,由于针对HIV感染机体并不