Primary exposure to SARS-CoV-2 variants elicits convergent epitope specificities, immunoglobulin V gene usage and public B cell clones

An important consequence of infection with a SARS-CoV-2 variant is protective humoral immunity against other variants. However, the basis for such cross-protection at the molecular level is incompletely understood. Here we characterized the repertoire and epitope specificity of antibodies elicited by infection with the Beta, Gamma and WA-1 ancestral variants and assessed their cross-reactivity to these and the more recent Delta and Omicron variants. We developed a method to obtain immunoglobulin sequences with concurrent rapid production and functional assessment of monoclonal antibodies from hundreds of single B cells sorted by flow cytometry. Infection with any variant elicited similar cross-binding antibody responses exhibiting a conserved hierarchy of epitope immunodominance. Furthermore, convergent V gene usage and similar public B cell clones were elicited regardless of infecting variant. These convergent responses despite antigenic variation may account for the continued efficacy of vaccines based on a single ancestral variant.

感染严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）变异株后的一项重要转归，是可诱导针对其他变异株的保护性体液免疫。然而，此类交叉保护作用的分子机制尚未完全明晰。本研究对Beta、Gamma及WA-1祖先毒株感染所诱导的抗体库及其表位特异性进行了表征，并评估了这些抗体对上述毒株以及近期出现的Delta和Omicron变异株的交叉反应性。我们开发了一种方法，可从数百个经流式细胞术（flow cytometry）分选的单个B细胞中获取免疫球蛋白序列，并同步快速制备单克隆抗体（monoclonal antibodies）并完成功能评估。任一毒株感染均可诱导出相似的交叉结合抗体应答，且表位免疫优势层级保守。此外，无论感染的毒株类型如何，均可诱导出趋同的V基因使用模式及相似的公共B细胞克隆。尽管存在抗原变异，但此类趋同应答或许可解释基于单一祖先毒株开发的疫苗为何仍能持续发挥保护效力。