Highly active engineered IgG3 antibodies against SARS-CoV-2.
Highly active engineered IgG3 antibodies against SARS-CoV-2.
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DOI：
10.1073/pnas.2107249118
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发表时间：
2021-10-01
影响因子：
11.1
通讯作者：
Steinkellner H
中科院分区：
文献类型：
--
作者：
Kallolimath S;Sun L;Palt R;Stiasny K;Mayrhofer P;Gruber C;Kogelmann B;Chen Q;Steinkellner H
有效中和SARS-CoV-2的单克隆抗体（mab）以前所未有的速度被开发出来。尽管如此，对于重链常数结构域诱导的抗原结合以外的各种Ab功能，人们的理解还很模糊。为了探索抗体在SARS-CoV-2免疫中的不同作用，我们利用糖工程的本菌烟草植物，在人血清中存在的四个IgG亚类（IgG1-4）中表达了SARS-CoV-2刺突蛋白（SP）结合单抗（H4）。所有四个亚类携带相同的抗原结合位点，在植物中完全组装，并表现出基本均匀的木糖和无焦糖糖基化谱。Ab变异体与SP结合，IgG3的结合活性增加了5倍。此外，所有H4亚型都能够中和SARS-CoV-2。然而，与其他亚类相比，H4-IgG3表现出高达50倍的优越中和效力。我们的数据表明IgG3抗体在SARS-CoV-2感染中具有很强的保护作用，并提示优越的中和作用可能是病毒表面SP交联的结果。在治疗和疫苗开发中应考虑到这一点。此外，我们强调了植物在紧急情况下快速表达复杂蛋白质的多种用途。
Monoclonal antibodies (mAbs) that efficiently neutralize SARS-CoV-2 have been developed at an unprecedented speed. Notwithstanding, there is a vague understanding of the various Ab functions induced beyond antigen binding by the heavy-chain constant domain. To explore the diverse roles of Abs in SARS-CoV-2 immunity, we expressed a SARS-CoV-2 spike protein (SP) binding mAb (H4) in the four IgG subclasses present in human serum (IgG1-4) using glyco-engineered Nicotiana benthamiana plants. All four subclasses, carrying the identical antigen-binding site, were fully assembled in planta and exhibited a largely homogeneous xylose- and fucose-free glycosylation profile. The Ab variants ligated to the SP with an up to fivefold increased binding activity of IgG3. Furthermore, all H4 subtypes were able to neutralize SARS-CoV-2. However, H4-IgG3 exhibited an up to 50-fold superior neutralization potency compared with the other subclasses. Our data point to a strong protective effect of IgG3 Abs in SARS-CoV-2 infection and suggest that superior neutralization might be a consequence of cross-linking the SP on the viral surface. This should be considered in therapy and vaccine development. In addition, we underscore the versatile use of plants for the rapid expression of complex proteins in emergency cases.
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影响因子：
64.5
作者：
Bournazos S;Gazumyan A;Seaman MS;Nussenzweig MC;Ravetch JV
通讯作者：
Ravetch JV
影响因子：
64.8
作者：
Ke, Zunlong;Oton, Joaquin;Briggs, John A. G.
通讯作者：
Briggs, John A. G.
影响因子：
82.9
作者：
Amanat F;Stadlbauer D;Strohmeier S;Nguyen THO;Chromikova V;McMahon M;Jiang K;Arunkumar GA;Jurczyszak D;Polanco J;Bermudez-Gonzalez M;Kleiner G;Aydillo T;Miorin L;Fierer DS;Lugo LA;Kojic EM;Stoever J;Liu STH;Cunningham-Rundles C;Felgner PL;Moran T;García-Sastre A;Caplivski D;Cheng AC;Kedzierska K;Vapalahti O;Hepojoki JM;Simon V;Krammer F
通讯作者：
Krammer F
影响因子：
3.9
作者：
Koblischke M;Traugott MT;Medits I;Spitzer FS;Zoufaly A;Weseslindtner L;Simonitsch C;Seitz T;Hoepler W;Puchhammer-Stöckl E;Aberle SW;Födinger M;Bergthaler A;Kundi M;Heinz FX;Stiasny K;Aberle JH
通讯作者：
Aberle JH
影响因子：
8
作者：
Liu, Li;Wei, Qiang;Chen, Zhiwei
通讯作者：
Chen, Zhiwei