Susceptibility of SARS-CoV-2 Omicron Variants to Therapeutic Monoclonal Antibodies: Systematic Review and Meta-analysis.
Susceptibility of SARS-CoV-2 Omicron Variants to Therapeutic Monoclonal Antibodies: Systematic Review and Meta-analysis.
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DOI：
10.1128/spectrum.00926-22
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发表时间：
2022-08-31
影响因子：
3.7
通讯作者：
Shafer, Robert W.
中科院分区：
文献类型：
--
作者：
Tao, Kaiming;Tzou, Philip L.;Pond, Sergei L. Kosakovsky;Ioannidis, John P. A.;Shafer, Robert W.
关键词：
新冠病毒奥密克戎变异株在其刺突受体结合域存在许多突变，该区域是所有已获批单克隆抗体（MAb）的作用靶点。确定奥密克戎变异株在多大程度上降低了单克隆抗体的敏感性对于新冠疫情的预防和治疗至关重要。我们系统检索了PubMed以及三个预印本服务器（截至2022年4月11日更新）中已获批单克隆抗体对奥密克戎变异株的体外活性相关研究。有51项研究符合要求，其中50项包含奥密克戎BA.1敏感性数据，17项包含奥密克戎BA.2敏感性数据。最早获批的两种单克隆抗体组合——巴尼韦单抗/埃特司韦单抗以及卡西瑞韦单抗/伊德维单抗，对奥密克戎BA.1和BA.2变异株基本无活性。在34项研究中，索托维单抗对奥密克戎BA.1的活性中位数降低了4.0倍（四分位距[IQR]：2.6 - 6.9）；在12项研究中，它对奥密克戎BA.2的活性中位数降低了17倍（IQR：13 - 30）。在15项研究中，西尔加维单抗/替沙格维单抗组合对奥密克戎BA.1的活性中位数降低了86倍（IQR：27 - 151）；在6项研究中，它对奥密克戎BA.2的活性中位数降低了5.4倍（IQR：3.7 - 6.9）。在8项针对奥密克戎BA.1的研究和6项针对奥密克戎BA.2的研究中，贝博妥珠单抗的活性没有降低。不同检测方法之间结果差异很大。对于已获批的单克隆抗体，野生型对照变异株的结果中有51/268（19.0%），奥密克戎BA.1和BA.2变异株的结果中有78/348（22.4%）比该单克隆抗体的中位数结果低4倍以上或高4倍以上。已发表的检测方法之间结果差异极大，这表明需要改进单克隆抗体敏感性检测的标准化或检测间校准。
重要性：针对新冠病毒刺突蛋白的单克隆抗体是预防和治疗新冠疫情最有效的措施之一。然而，新冠病毒奥密克戎变异株在其刺突受体结合域包含许多突变，而这是所有已获批单克隆抗体的作用靶点。因此，确定奥密克戎变异株在多大程度上降低了单克隆抗体的敏感性对于新冠疫情的预防和治疗至关重要。我们确定了51项研究，这些研究报告了两种主要的奥密克戎变异株BA.1和BA.2对处于临床研发后期的治疗性单克隆抗体的体外敏感性，包括8种已获批的单克隆抗体和3种已获批的单克隆抗体组合。我们评估了不同单克隆抗体对奥密克戎变异株活性降低的程度。许多单克隆抗体对奥密克戎变异株活性的显著丧失凸显了开发针对刺突蛋白保守区域的单克隆抗体的重要性。检测方法之间结果差异极大表明需要改进单克隆抗体敏感性检测的标准化。
SARS-CoV-2 Omicron variants contain many mutations in its spike receptor-binding domain, the target of all authorized monoclonal antibodies (MAbs). Determining the extent to which Omicron variants reduced MAb susceptibility is critical to preventing and treating COVID-19. We systematically reviewed PubMed and three preprint servers, last updated 11 April 2022, for the in vitro activity of authorized MAbs against the Omicron variants. Fifty-one studies were eligible, including 50 containing Omicron BA.1 susceptibility data and 17 containing Omicron BA.2 susceptibility data. The first two authorized MAb combinations, bamlanivimab/etesevimab and casirivimab/imdevimab, were largely inactive against the Omicron BA.1 and BA.2 variants. In 34 studies, sotrovimab displayed a median 4.0-fold (interquartile range [IQR]: 2.6 to 6.9) reduction in activity against Omicron BA.1, and in 12 studies, it displayed a median 17-fold (IQR: 13 to 30) reduction in activity against Omicron BA.2. In 15 studies, the combination cilgavimab/tixagevimab displayed a median 86-fold (IQR: 27 to 151) reduction in activity against Omicron BA.1, and in six studies, it displayed a median 5.4-fold (IQR: 3.7 to 6.9) reduction in activity against Omicron BA.2. In eight studies against Omicron BA.1 and six studies against Omicron BA.2, bebtelovimab displayed no reduction in activity. Disparate results between assays were common. For authorized MAbs, 51/268 (19.0%) results for wild-type control variants and 78/348 (22.4%) results for Omicron BA.1 and BA.2 variants were more than 4-fold below or 4-fold above the median result for that MAb. Highly disparate results between published assays indicate a need for improved MAb susceptibility test standardization or interassay calibration. IMPORTANCE Monoclonal antibodies (MAbs) targeting the SARS-CoV-2 spike protein are among the most effective measures for preventing and treating COVID-19. However, SARS-CoV-2 Omicron variants contain many mutations in their spike receptor-binding domains, the target of all authorized MAbs. Therefore, determining the extent to which Omicron variants reduced MAb susceptibility is critical to preventing and treating COVID-19. We identified 51 studies that reported the in vitro susceptibility of the two main Omicron variants BA.1 and BA.2 to therapeutic MAbs in advanced clinical development, including eight authorized individual MAbs and three authorized MAb combinations. We estimated the degree to which different MAbs displayed reduced activity against Omicron variants. The marked loss of activity of many MAbs against Omicron variants underscores the importance of developing MAbs that target conserved regions of spike. Highly disparate results between assays indicate the need for improved MAb susceptibility test standardization.
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影响因子：
64.8
作者：
Barnes CO;Jette CA;Abernathy ME;Dam KA;Esswein SR;Gristick HB;Malyutin AG;Sharaf NG;Huey-Tubman KE;Lee YE;Robbiani DF;Nussenzweig MC;West AP Jr;Bjorkman PJ
通讯作者：
Bjorkman PJ
影响因子：
64.5
作者：
Dejnirattisai W;Zhou D;Ginn HM;Duyvesteyn HME;Supasa P;Case JB;Zhao Y;Walter TS;Mentzer AJ;Liu C;Wang B;Paesen GC;Slon-Campos J;López-Camacho C;Kafai NM;Bailey AL;Chen RE;Ying B;Thompson C;Bolton J;Fyfe A;Gupta S;Tan TK;Gilbert-Jaramillo J;James W;Knight M;Carroll MW;Skelly D;Dold C;Peng Y;Levin R;Dong T;Pollard AJ;Knight JC;Klenerman P;Temperton N;Hall DR;Williams MA;Paterson NG;Bertram FKR;Siebert CA;Clare DK;Howe A;Radecke J;Song Y;Townsend AR;Huang KA;Fry EE;Mongkolsapaya J;Diamond MS;Ren J;Stuart DI;Screaton GR
通讯作者：
Screaton GR
DOI：
10.1038/s41577-020-00471-1
发表时间：
2020-12
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Khoury DS;Wheatley AK;Ramuta MD;Reynaldi A;Cromer D;Subbarao K;O'Connor DH;Kent SJ;Davenport MP
通讯作者：
Davenport MP
影响因子：
64.5
作者：
Hoffmann M;Krüger N;Schulz S;Cossmann A;Rocha C;Kempf A;Nehlmeier I;Graichen L;Moldenhauer AS;Winkler MS;Lier M;Dopfer-Jablonka A;Jäck HM;Behrens GMN;Pöhlmann S
通讯作者：
Pöhlmann S
影响因子：
64.5
作者：
Cui Z;Liu P;Wang N;Wang L;Fan K;Zhu Q;Wang K;Chen R;Feng R;Jia Z;Yang M;Xu G;Zhu B;Fu W;Chu T;Feng L;Wang Y;Pei X;Yang P;Xie XS;Cao L;Cao Y;Wang X
通讯作者：
Wang X