Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Viruses. 2021 Oct 6;13(10):2009. doi: 10.3390/v13102009.
The evolution of mutations in SARS-CoV-2 at antigenic sites that impact neutralizing antibody responses in humans poses a risk to immunity developed through vaccination and natural infection. The highly successful RNA-based vaccines have enabled rapid vaccine updates that incorporate mutations from current variants of concern (VOCs). It is therefore important to anticipate future antigenic mutations as the virus navigates the heterogeneous global landscape of host immunity. Toward this goal, we survey epitope-paratope interfaces of anti-SARS-CoV-2 antibodies to map an antigenic space that captures the role of each spike protein residue within the polyclonal antibody response directed against the ACE2-receptor binding domain (RBD) or the N-terminal domain (NTD). In particular, the antigenic space map builds on recently published epitope definitions by annotating epitope overlap and orthogonality at the residue level. We employ the antigenic space map as a framework to understand how mutations on nine major variants contribute to each variant's evasion of neutralizing antibodies. Further, we identify constellations of mutations that span the orthogonal epitope regions of the RBD and NTD on the variants with the greatest antibody escape. Finally, we apply the antigenic space map to predict which regions of antigenic space-should they mutate-may be most likely to complementarily augment antibody evasion for the most evasive and transmissible VOCs.
SARS-CoV-2 抗原位点突变的进化会影响人类中和抗体反应，从而对通过疫苗接种和自然感染产生的免疫构成威胁。高度成功的基于 RNA 的疫苗能够快速更新疫苗，纳入当前关注变体 (VOC) 的突变。因此，重要的是要预测未来的抗原突变，因为病毒在宿主免疫的异质全球景观中导航。为此，我们调查了抗 SARS-CoV-2 抗体的表位-互补位界面，以绘制一个抗原空间，该空间捕获了针对 ACE2 受体结合域 (RBD) 或 N 端结构域 (NTD) 的多克隆抗体反应中每个刺突蛋白残基的作用。特别是，抗原空间图基于最近发表的表位定义，通过在残基水平注释表位重叠和正交性来构建。我们将抗原空间图用作框架，以了解九个主要变体上的突变如何导致每种变体逃避中和抗体。此外，我们确定了跨越 RBD 和 NTD 的正交表位区域的突变组合，这些变体的抗体逃逸能力最强。最后，我们应用抗原空间图来预测如果发生突变，抗原空间的哪些区域最有可能互补地增强最具逃逸性和传染性的 VOC 的抗体逃逸。
