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在抗体介导预防试验中,VRC01在获取后选择罕见的HIV逃生突变

Carolyn Williamson^1,2,3, Lyle Curry¹, Nonhlanhla N Mkhize^4,5

¹Division of Medical Virology, Institute of Infectious Disease and Molecular Medicine and Wellcome CIDRI-Africa Centre, Faculty of Health Sciences, University of Cape Town. Cape Town, South Africa.

bioRxiv : the preprint server for biology

|November 24, 2025

概括

像VRC01这样的广泛中和抗体 (bnAbs) 显示出对预防艾滋病毒的希望. 然而,这项研究发现VRC01可以在感染后选择病毒逃生突变,突出显示需要更强大的艾滋病毒预防策略.

科学领域:

免疫学免疫学免疫学
病毒学病毒学
传染性疾病传染性疾病

背景情况:

广泛中和抗体 (bnAbs) 对艾滋病毒预防策略至关重要.
CD4结合部位 (CD4bs) bnAb VRC01已经显示出对敏感的HIV菌株的有效性.
了解bnAb压力下的病毒演变是改善艾滋病毒预防的关键.

研究的目的:

调查预防性VRC01给药对艾滋病毒获取后演变的影响.
为了识别和描述由VRC01.01选择的病毒逃生突变.
评估与其他bnAbs.相比,这些逃逸突变的交叉电阻概况.

主要方法:

分析了来自抗体介导预防 (AMP) 试验参与者的超过12,000个艾滋病毒发酵序列.
在VRC01治疗和安慰剂组中识别de novo突变.
评估全球艾滋病毒株的突变频率和对其他CD4bs bnAbs的交叉耐药性.

主要成果:

在26名接受治疗的参与者中,在8名中发现了VRC01介导的脱离突变,但在21名安慰剂参与者中没有发现任何突变.
这些在全球低频率 (<1%) 发现的脱离突变主要发生在Env Loop-D和β23/V5区域.
突变使一些CD4bs bnAbs产生交叉抗性,但强大的bnAbs如N6和1-18在很大程度上保持了活性.

结论:

预防性VRC01可以选择感染后的HIV逃生突变.
需要具有更广泛和更强大的活性的下一代bnAbs来实现持久有效的基于抗体的HIV预防.
针对保存的病毒表位仍然是艾滋病毒疫苗和治疗开发的关键目标.

关键词:

艾滋病病毒艾滋病病毒艾滋病病毒艾滋病毒VRC01逃生突变在VRC01的阻力.抗体介导预防抗体介导预防广泛中和抗体 (bnAbs) 是一种抗体.

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