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Nature:SARS-CoV-2的RBD抗体具有很大限度的抗病毒逃逸能力 

2021-07-14 haibei MedSci原创

从长远来看,一个理想的抗SARS-CoV-2抗体应该具备抵抗病毒逃逸的能力,并对不同的SARS相关冠状病毒(sarbecoviruses病毒)有活性。

目前,针对SARS-CoV-2最有效的中和抗体--包括那些在临床上使用的抗体和在多克隆血清中占主导地位的抗体--是针对刺突蛋白受体结合域(RBD)的抗体。随着新冠的流行,在SARS-CoV-2的变体中出现了抵抗抗体结合的RBD突变,这突出表明了我们需要开发设计具有对抗病毒逃逸能力的抗体和疫苗。

在已有的研究中,人们曾描述过一种抗体,S3094,它表现出强大的效应功能,并能中和目前所有的SARS-CoV-2变体和sarbecovirus分支的SARS-CoV-1。S309构成了一种抗体疗法(VIR-7831,最近更名为sotrovimab)的基础,该疗法已获得FDA的紧急使用授权,用于治疗COVID-19

从长远来看,一个理想的抗SARS-CoV-2抗体应该具备抵抗病毒逃逸的能力,并对不同的SARS相关冠状病毒(sarbecoviruses病毒)有活性,它可以通过病毒中和以及效应器功能而展现出高度的保护力。系统了解这些特性之间的关系以及不同表位之间的差异将有助于开发抗体疗法并指导疫苗设计。

最近,研究人员全面描述了针对受体结合域(RBD)的SARS-CoV-2抗体的坑逃逸能力、广度和效力。尽管抗体的体外中和效力和与sarbecoviruses结合的广度之间存在权衡,但研究人员鉴定出了一类中和抗体,其具有特殊的sarbecoviruses广度和对SARS-CoV-2逃逸的相应抵抗力。其中一种抗体,S2H97,在所有的sarbecoviruses支系中都有很高的亲和力,其与以前未描述的隐性表位结合预防性地保护仓鼠免受病毒挑战。

抗体的表位、效力、广度和逃逸性

靶向ACE2受体结合域(RBM)的抗体尽管中和效力很高,但它们通常具有较差的广度,很容易被突变病毒所逃脱。而在该研究中,研究人员描述了一种有效的RBM抗体(S2E128),它在与SARS-CoV-2相关的sarbecoviruses中具有很好的广度,并且对病毒逃逸具有较高的抵抗。

总之,这些数据突出了针对RBD的抗体在逃逸、广度和效力方面的基本原则,并确定了针对当前和未来潜在的大流行病时,抗体设计的优先表位和特征。

 

原始出处:

Tyler N. Starr et al. SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape. Nature (2021). 

 

 

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    2021-09-17 hukaixun
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    2022-03-29 liye789132251
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    2021-07-16 yahu
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    2021-07-16 小刀医生

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