Institute for Medical Virology, University Hospital Frankfurt, Goethe University Frankfurt, 60596 Frankfurt am Main, Germany.
Institute for Medical Virology, University Hospital Frankfurt, Goethe University Frankfurt, 60596 Frankfurt am Main, Germany.
EBioMedicine. 2022 Aug;82:104158. doi: 10.1016/j.ebiom.2022.104158. Epub 2022 Jul 11.
In recent months, Omicron variants of SARS-CoV-2 have become dominant in many regions of the world, and case numbers with Omicron subvariants BA.1 and BA.2 continue to increase. Due to numerous mutations in the spike protein, the efficacy of currently available vaccines, which are based on Wuhan-Hu 1 isolate of SARS-CoV-2, is reduced, leading to breakthrough infections. Efficacy of monoclonal antibody therapy is also likely impaired.
In our in vitro study using A549-AT cells constitutively expressing ACE2 and TMPRSS2, we determined and compared the neutralizing capacity of vaccine-elicited sera, convalescent sera and monoclonal antibodies against authentic SARS-CoV-2 Omicron BA.1 and BA.2 compared with Delta.
Almost no neutralisation of Omicron BA.1 and BA.2 was observed using sera from individuals vaccinated with two doses 6 months earlier, regardless of the type of vaccine taken. Shortly after the booster dose, most sera from triple BNT162b2-vaccinated individuals were able to neutralise both Omicron variants. In line with waning antibody levels three months after the booster, only weak residual neutralisation was observed for BA.1 (26%, n = 34, 0 median NT) and BA.2 (44%, n = 34, 0 median NT). In addition, BA.1 but not BA.2 was resistant to the neutralising monoclonal antibodies casirivimab/imdevimab, while BA.2 exhibited almost a complete evasion from the neutralisation induced by sotrovimab.
Both SARS-CoV-2 Omicron subvariants BA.1 and BA.2 escape antibody-mediated neutralisation elicited by vaccination, previous infection with SARS-CoV-2, and monoclonal antibodies. Waning immunity renders the majority of tested sera obtained three months after booster vaccination negative in BA.1 and BA.2 neutralisation. Omicron subvariant specific resistance to the monoclonal antibodies casirivimab/imdevimab and sotrovimab emphasizes the importance of genotype-surveillance and guided application.
This study was supported in part by the Goethe-Corona-Fund of the Goethe University Frankfurt (M.W.) and the Federal Ministry of Education and Research (COVIDready; grant 02WRS1621C (M.W.).
近几个月来，SARS-CoV-2 的奥密克戎变体在世界许多地区成为优势毒株，并且奥密克戎 BA.1 和 BA.2 亚变体的病例数量持续增加。由于刺突蛋白的大量突变，目前基于 SARS-CoV-2 的武汉-Hu1 分离株的疫苗效力降低，导致突破性感染。单克隆抗体治疗的疗效也可能受损。
在我们使用 A549-AT 细胞进行的体外研究中，我们比较了疫苗接种后血清、恢复期血清和针对真实 SARS-CoV-2 奥密克戎 BA.1 和 BA.2 与 Delta 的单克隆抗体的中和能力。
即使在加强剂量后不久，接受三剂 BNT162b2 疫苗接种的个体的大多数血清也能够中和这两种奥密克戎变体。与加强剂量后三个月抗体水平下降一致，仅观察到对 BA.1（26%，n=34，0 中位数 NT）和 BA.2（44%，n=34，0 中位数 NT）的微弱残留中和作用。此外，BA.1 但不是 BA.2 对中和单克隆抗体 casirivimab/imdevimab 有抗性，而 BA.2 对 sotrovimab 诱导的中和作用几乎完全逃避。
SARS-CoV-2 的奥密克戎亚变体 BA.1 和 BA.2 逃避了由疫苗接种、以前的 SARS-CoV-2 感染和单克隆抗体引起的抗体介导的中和。免疫力下降使大多数在加强接种后三个月获得的血清在 BA.1 和 BA.2 中和中呈阴性。奥密克戎亚变体对单克隆抗体 casirivimab/imdevimab 和 sotrovimab 的特异性耐药性强调了基因型监测和指导应用的重要性。
这项研究部分得到法兰克福歌德大学歌德冠状病毒基金（M.W.）和联邦教育和研究部（COVIDready；资助 02WRS1621C（M.W.）的支持。
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