IgG-like bispecific antibodies with potent and synergistic neutralization against circulating SARS-CoV-2 variants of concern.
IgG-like bispecific antibodies with potent and synergistic neutralization against circulating SARS-CoV-2 variants of concern.
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DOI：
10.1038/s41467-022-33030-4
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发表时间：
2022-10-03
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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作者：
单克隆抗体是治疗COVID-19的一种有前途的方法，然而SARS-CoV-2变异体的出现对这些疗法的疗效和未来提出了挑战。抗体鸡尾酒被用来缓解这些挑战，但中和逃逸仍然是一个主要的挑战，需要替代策略。在这里，我们提出了两个抗SARS-CoV-2刺突结合抗体，一类和一类4，从我们的非免疫人单链可变片段（scFv）噬菌体文库中选择，它们被工程化为四个完全人IgG样双特异性抗体（BsAb）。hACE 2小鼠的预防和金黄仓鼠的感染后治疗证明了单特异性抗体对原始武汉毒株的有效性，而BsAb的有希望的体外结果证明了对关注的循环变体的中和活性的增强的结合和明显的协同作用。特别地，一种以串联scFv-Fc构型工程化的BsAb显示针对包括B.1.617.2的几种关注变体的协同中和活性。这项工作提供的证据表明，可以使用BsAb支架实现协同中和，并作为未来开发广泛反应性BsAb的基础，以对抗新出现的令人担忧的变体。COVID-19可以用抗SARS-CoV-2的单克隆抗体治疗，但出现的新变体可能对现有疗法产生耐药性。在此，作者表明，抗SARS-CoV-2刺突人单链抗体片段在工程化为人双特异性抗体后可获得针对所关注变体的中和活性。
Monoclonal antibodies are a promising approach to treat COVID-19, however the emergence of SARS-CoV-2 variants has challenged the efficacy and future of these therapies. Antibody cocktails are being employed to mitigate these challenges, but neutralization escape remains a major challenge and alternative strategies are needed. Here we present two anti-SARS-CoV-2 spike binding antibodies, one Class 1 and one Class 4, selected from our non-immune human single-chain variable fragment (scFv) phage library, that are engineered into four, fully-human IgG-like bispecific antibodies (BsAb). Prophylaxis of hACE2 mice and post-infection treatment of golden hamsters demonstrates the efficacy of the monospecific antibodies against the original Wuhan strain, while promising in vitro results with the BsAbs demonstrate enhanced binding and distinct synergistic effects on neutralizing activity against circulating variants of concern. In particular, one BsAb engineered in a tandem scFv-Fc configuration shows synergistic neutralization activity against several variants of concern including B.1.617.2. This work provides evidence that synergistic neutralization can be achieved using a BsAb scaffold, and serves as a foundation for the future development of broadly reactive BsAbs against emerging variants of concern. COVID-19 can be treated with monoclonal antibodies against SARS-CoV-2, but emerging new variants might show resistance towards existing therapy. Here authors show that anti-SARS-CoV-2 spike human single-chain antibody fragments could gain neutralizing activity against variants of concern upon engineering into a human bispecific antibody.
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影响因子：
64.5
作者：
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通讯作者：
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影响因子：
64.5
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两种抗体鸡尾酒中和中和的遗传和结构基础。
影响因子：
28.3
作者：
Dong J;Zost SJ;Greaney AJ;Starr TN;Dingens AS;Chen EC;Chen RE;Case JB;Sutton RE;Gilchuk P;Rodriguez J;Armstrong E;Gainza C;Nargi RS;Binshtein E;Xie X;Zhang X;Shi PY;Logue J;Weston S;McGrath ME;Frieman MB;Brady T;Tuffy KM;Bright H;Loo YM;McTamney PM;Esser MT;Carnahan RH;Diamond MS;Bloom JD;Crowe JE Jr
通讯作者：
Crowe JE Jr
影响因子：
64.5
作者：
Hoffmann M;Arora P;Groß R;Seidel A;Hörnich BF;Hahn AS;Krüger N;Graichen L;Hofmann-Winkler H;Kempf A;Winkler MS;Schulz S;Jäck HM;Jahrsdörfer B;Schrezenmeier H;Müller M;Kleger A;Münch J;Pöhlmann S
通讯作者：
Pöhlmann S
影响因子：
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作者：
Ahmad ZA;Yeap SK;Ali AM;Ho WY;Alitheen NB;Hamid M
通讯作者：
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