Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
Department of Genome Sciences & Medical Scientist Training Program, University of Washington, Seattle, Washington, United States of America.
PLoS Pathog. 2022 Feb 8;18(2):e1010248. doi: 10.1371/journal.ppat.1010248. eCollection 2022 Feb.
Many SARS-CoV-2 variants have mutations at key sites targeted by antibodies. However, it is unknown if antibodies elicited by infection with these variants target the same or different regions of the viral spike as antibodies elicited by earlier viral isolates. Here we compare the specificities of polyclonal antibodies produced by humans infected with early 2020 isolates versus the B.1.351 variant of concern (also known as Beta or 20H/501Y.V2), which contains mutations in multiple key spike epitopes. The serum neutralizing activity of antibodies elicited by infection with both early 2020 viruses and B.1.351 is heavily focused on the spike receptor-binding domain (RBD). However, within the RBD, B.1.351-elicited antibodies are more focused on the "class 3" epitope spanning sites 443 to 452, and neutralization by these antibodies is notably less affected by mutations at residue 484. Our results show that SARS-CoV-2 variants can elicit polyclonal antibodies with different immunodominance hierarchies.
许多 SARS-CoV-2 变体在抗体靶向的关键位点发生突变。然而，目前尚不清楚感染这些变体后产生的抗体是否与早期病毒分离株产生的抗体靶向病毒刺突的相同或不同区域。在这里，我们比较了 2020 年初感染早期分离株和关注变体（也称为 Beta 或 20H/501Y.V2）的人类产生的多克隆抗体的特异性，该变体包含多个关键刺突表位的突变。感染早期 2020 年病毒和 B.1.351 产生的抗体的血清中和活性主要集中在刺突受体结合域（RBD）。然而，在 RBD 内，B.1.351 诱导的抗体更集中在跨越 443 到 452 位的“类 3”表位，并且这些抗体的中和作用受 484 位残基突变的影响明显较小。我们的研究结果表明，SARS-CoV-2 变体可以诱导具有不同免疫优势层次的多克隆抗体。
