Biparatopic antibody BA7208/7125 effectively neutralizes SARS-CoV-2 variants including Omicron BA.1-BA.5.
Biparatopic antibody BA7208/7125 effectively neutralizes SARS-CoV-2 variants including Omicron BA.1-BA.5.
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双互补位抗体 BA7208/7125 有效中和 SARS-CoV-2 变体，包括 Omicron BA.1-BA.5
DOI：
10.1038/s41421-022-00509-9
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发表时间：
2023-01-07
期刊：
影响因子：
33.5
通讯作者：
Zhao, Jincun
中科院分区：
文献类型：
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作者：
Wang, Yanqun;Yan, An;Song, Deyong;Dong, Chuangchuang;Rao, Muding;Gao, Yuanzhu;Qi, Ruxi;Ma, Xiaomin;Wang, Qiaoping;Xu, Hongguang;Liu, Hong;Han, Jing;Duan, Maoqin;Liu, Shuo;Yu, Xiaoping;Zong, Mengqi;Feng, Jianxia;Jiao, Jie;Zhang, Huimin;Li, Min;Yu, Beibei;Wang, Yanxia;Meng, Fanhao;Ni, Xiaodan;Li, Ying;Shen, Zhenduo;Sun, Baiping;Shao, Xin;Zhao, Haifeng;Zhao, Yanyan;Li, Rui;Zhang, Yanan;Du, Guangying;Lu, Jun;You, Chunna;Jiang, Hua;Zhang, Lu;Wang, Lan;Dou, Changlin;Liu, Zheng;Zhao, Jincun
SARS-CoV-2 Omicron亚变体已被证明可广泛逃避为临床使用而开发的单克隆抗体（mAb），这迫切需要开发新的广谱mAb。在这里，我们报告了两个抗RBD中和抗体BA 7208和BA 7125的分离和分析，从小鼠工程生产人类抗体。虽然BA 7125对除Omicron亚系之外的所有变体显示出广泛的中和活性，但BA 7208对除Mu之外的所有测试的SARS-CoV-2变体（包括Omicron BA.1-BA.5）具有强效中和作用。通过将BA 7208和BA 7125通过knobs-into-holes技术结合，我们产生了能够中和所有测试的循环SARS-CoV-2变体的双互补位抗体BA 7208/7125。与三聚体Delta和Omicron刺突复合的这些广谱抗体的冷冻电子显微镜结构表明，接触残基是高度保守的，并且与当前变体的RBD中的突变残基具有最小的相互作用。此外，我们发现，通过腹膜内、鼻内或雾化吸入途径给予BA 7208/7125在hACE 2转基因和野生型小鼠中显示出对Omicron BA. 1和BA. 2的有效治疗效果，并分别显示出有效的预防作用。因此，BA 7208/7125有可能成为一种有效的候选抗COVID-19干预药物。
SARS-CoV-2 Omicron subvariants have demonstrated extensive evasion from monoclonal antibodies (mAbs) developed for clinical use, which raises an urgent need to develop new broad-spectrum mAbs. Here, we report the isolation and analysis of two anti-RBD neutralizing antibodies BA7208 and BA7125 from mice engineered to produce human antibodies. While BA7125 showed broadly neutralizing activity against all variants except the Omicron sublineages, BA7208 was potently neutralizing against all tested SARS-CoV-2 variants (including Omicron BA.1–BA.5) except Mu. By combining BA7208 and BA7125 through the knobs-into-holes technology, we generated a biparatopic antibody BA7208/7125 that was able to neutralize all tested circulating SARS-CoV-2 variants. Cryo-electron microscopy structure of these broad-spectrum antibodies in complex with trimeric Delta and Omicron spike indicated that the contact residues are highly conserved and had minimal interactions with mutational residues in RBD of current variants. In addition, we showed that administration of BA7208/7125 via the intraperitoneal, intranasal, or aerosol inhalation route showed potent therapeutic efficacy against Omicron BA.1 and BA.2 in hACE2-transgenic and wild-type mice and, separately, effective prophylaxis. BA7208/7125 thus has the potential to be an effective candidate as an intervention against COVID-19.
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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
可吸入双特异性单域抗体广泛中和 SARS-CoV-2 变体
影响因子：
64.5
作者：
Li C;Zhan W;Yang Z;Tu C;Hu G;Zhang X;Song W;Du S;Zhu Y;Huang K;Kong Y;Zhang M;Mao Q;Gu X;Zhang Y;Xie Y;Deng Q;Song Y;Chen Z;Lu L;Jiang S;Wu Y;Sun L;Ying T
通讯作者：
Ying T
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：
17.1
作者：
Jones BE;Brown-Augsburger PL;Corbett KS;Westendorf K;Davies J;Cujec TP;Wiethoff CM;Blackbourne JL;Heinz BA;Foster D;Higgs RE;Balasubramaniam D;Wang L;Zhang Y;Yang ES;Bidshahri R;Kraft L;Hwang Y;Žentelis S;Jepson KR;Goya R;Smith MA;Collins DW;Hinshaw SJ;Tycho SA;Pellacani D;Xiang P;Muthuraman K;Sobhanifar S;Piper MH;Triana FJ;Hendle J;Pustilnik A;Adams AC;Berens SJ;Baric RS;Martinez DR;Cross RW;Geisbert TW;Borisevich V;Abiona O;Belli HM;de Vries M;Mohamed A;Dittmann M;Samanovic MI;Mulligan MJ;Goldsmith JA;Hsieh CL;Johnson NV;Wrapp D;McLellan JS;Barnhart BC;Graham BS;Mascola JR;Hansen CL;Falconer E
通讯作者：
Falconer E
DOI：
10.3390/v14020294
发表时间：
2022-01-30
期刊：
Viruses
影响因子：
--
作者：
Grabowski F;Kochańczyk M;Lipniacki T
通讯作者：
Lipniacki T