Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Vir Biotechnology, San Francisco, CA 94158, USA.
Science. 2022 Aug 19;377(6608):890-894. doi: 10.1126/science.abq0203. Epub 2022 Jul 19.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern comprises several sublineages, with BA.2 and BA.2.12.1 having replaced the previously dominant BA.1 and with BA.4 and BA.5 increasing in prevalence worldwide. We show that the large number of Omicron sublineage spike mutations leads to enhanced angiotensin-converting enzyme 2 (ACE2) binding, reduced fusogenicity, and severe dampening of plasma neutralizing activity elicited by infection or seven clinical vaccines relative to the ancestral virus. Administration of a homologous or heterologous booster based on the Wuhan-Hu-1 spike sequence markedly increased neutralizing antibody titers and breadth against BA.1, BA.2, BA.2.12.1, BA.4, and BA.5 across all vaccines evaluated. Our data suggest that although Omicron sublineages evade polyclonal neutralizing antibody responses elicited by primary vaccine series, vaccine boosters may provide sufficient protection against Omicron-induced severe disease.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的奥密克戎关切变异株包含多个亚谱系，其中 BA.2 和 BA.2.12.1 已经取代了之前占主导地位的 BA.1，而 BA.4 和 BA.5 在全球的流行率正在上升。我们表明，奥密克戎亚谱系刺突突变的大量存在导致血管紧张素转换酶 2（ACE2）结合增强、融合性降低，以及与原始病毒相比，感染或七种临床疫苗引起的血浆中和活性严重减弱。基于武汉-Hu-1 刺突序列的同源或异源加强剂显著提高了针对 BA.1、BA.2、BA.2.12.1、BA.4 和 BA.5 的中和抗体滴度和广度，所有评估的疫苗均如此。我们的数据表明，尽管奥密克戎亚谱系逃避了由初级疫苗系列引起的多克隆中和抗体反应，但疫苗加强剂可能为针对奥密克戎引起的严重疾病提供足够的保护。
