PDF(Pubmed)
Abstract：
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages of the Omicron variant rapidly became dominant in early 2022 and frequently cause human infections despite vaccination or prior infection with other variants. In addition to antibody-evading mutations in the receptor-binding domain, Omicron features amino acid mutations elsewhere in the Spike protein; however, their effects generally remain ill defined. The Spike D796Y substitution is present in all Omicron sub-variants and occurs at the same site as a mutation (D796H) selected during viral evolution in a chronically infected patient. Here, we map antibody reactivity to a linear epitope in the Spike protein overlapping position 796. We show that antibodies binding this region arise in pre-Omicron SARS-CoV-2 convalescent and vaccinated subjects but that both D796Y and D796H abrogate their binding. These results suggest that D796Y contributes to the fitness of Omicron in hosts with pre-existing immunity to other variants of SARS-CoV-2 by evading antibodies targeting this site.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved substantially through the coronavirus disease 2019 (COVID-19) pandemic: understanding the drivers and consequences of this evolution is essential for projecting the course of the pandemic and developing new countermeasures. Here, we study the immunological effects of a particular mutation present in the Spike protein of all Omicron strains and find that it prevents the efficient binding of a class of antibodies raised by pre-Omicron vaccination and infection. These findings reveal a novel consequence of a poorly understood Omicron mutation and shed light on the drivers and effects of SARS-CoV-2 evolution.
摘要：
目标：严重急性呼吸道综合症冠状病毒2（SARS-CoV-2）在2019年冠状病毒病（COVID-19）大流行中发生了实质性的演变：了解这种演变的驱动因素和后果对于预测大流行的过程和开发新的对策至关重要。这里,我们研究了所有Omicron菌株的Spike蛋白中存在的特定突变的免疫学效应,发现该突变阻止了由Omicron疫苗接种和感染产生的一类抗体的有效结合.这些发现揭示了对Omicron突变知之甚少的新结果，并揭示了SARS-CoV-2进化的驱动因素和影响。
