Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution.
Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution.
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DOI：
10.1038/s41586-022-05644-7
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发表时间：
2023-03
期刊：
影响因子：
64.8
通讯作者：
Xie, Xiaoliang Sunney
中科院分区：
文献类型：
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作者：
Cao, Yunlong;Jian, Fanchong;Wang, Jing;Yu, Yuanling;Song, Weiliang;Yisimayi, Ayijiang;Wang, Jing;An, Ran;Chen, Xiaosu;Zhang, Na;Wang, Yao;Wang, Peng;Zhao, Lijuan;Sun, Haiyan;Yu, Lingling;Yang, Sijie;Niu, Xiao;Xiao, Tianhe;Gu, Qingqing;Shao, Fei;Hao, Xiaohua;Xu, Yanli;Jin, Ronghua;Shen, Zhongyang;Wang, Youchun;Xie, Xiaoliang Sunney
Omicron 的不断发展导致了众多变体的快速同时出现，这些变体比 BA.5 显示出增长优势（参考文献 ）。尽管它们的进化过程各不相同，但它们的受体结合域（RBD）的突变集中在几个热点上。这种突然趋同进化的驱动力和目的地及其对体液免疫的影响仍不清楚。在这里，我们证明这些趋同突变可以导致中和抗体药物和恢复期血浆（包括来自 BA.5 突破性感染的血浆）的逃避，同时保持足够的 ACE2 结合能力。 BQ.1.1.10 (BQ.1.1 + Y144del)、BA.4.6.3、XBB 和 CH.1.1 是所测试的抗体逃避程度最高的菌株。为了描述趋同进化的起源，我们确定了从 BA.2 和 BA.5 突破性感染个体中分离出的单克隆抗体的逃逸突变谱和中和活性。由于体液免疫印记，BA.2，尤其是 BA.5 突破性感染减少了中和抗体结合位点的多样性，并增加了非中和抗体克隆的比例，这反过来又集中了体液免疫压力并促进了 RBD 的趋同进化。此外，我们表明，通过深度突变扫描图谱可以准确推断收敛的 RBD 突变，并且通过构建收敛的假病毒突变体可以很好地预见 BA.2.75 和 BA.5 亚变体的进化趋势。这些结果表明，当前的群体免疫和 BA.5 疫苗加强剂可能无法有效预防 Omicron 趋同变种的感染。 SARS-CoV-2 Omicron 受体结合域热点的趋同突变可导致免疫逃避并维持足够的 ACE2 结合能力。
Continuous evolution of Omicron has led to a rapid and simultaneous emergence of numerous variants that display growth advantages over BA.5 (ref. ). Despite their divergent evolutionary courses, mutations on their receptor-binding domain (RBD) converge on several hotspots. The driving force and destination of such sudden convergent evolution and its effect on humoral immunity remain unclear. Here we demonstrate that these convergent mutations can cause evasion of neutralizing antibody drugs and convalescent plasma, including those from BA.5 breakthrough infection, while maintaining sufficient ACE2-binding capability. BQ.1.1.10 (BQ.1.1 + Y144del), BA.4.6.3, XBB and CH.1.1 are the most antibody-evasive strains tested. To delineate the origin of the convergent evolution, we determined the escape mutation profiles and neutralization activity of monoclonal antibodies isolated from individuals who had BA.2 and BA.5 breakthrough infections. Owing to humoral immune imprinting, BA.2 and especially BA.5 breakthrough infection reduced the diversity of the neutralizing antibody binding sites and increased proportions of non-neutralizing antibody clones, which, in turn, focused humoral immune pressure and promoted convergent evolution in the RBD. Moreover, we show that the convergent RBD mutations could be accurately inferred by deep mutational scanning profiles, and the evolution trends of BA.2.75 and BA.5 subvariants could be well foreseen through constructed convergent pseudovirus mutants. These results suggest that current herd immunity and BA.5 vaccine boosters may not efficiently prevent the infection of Omicron convergent variants. Convergent mutations in hotspots of the SARS-CoV-2 Omicron receptor-binding domain can cause immune evasion and maintain sufficient ACE2-binding capability.
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影响因子：
16.6
作者：
Greaney AJ;Starr TN;Barnes CO;Weisblum Y;Schmidt F;Caskey M;Gaebler C;Cho A;Agudelo M;Finkin S;Wang Z;Poston D;Muecksch F;Hatziioannou T;Bieniasz PD;Robbiani DF;Nussenzweig MC;Bjorkman PJ;Bloom JD
通讯作者：
Bloom JD
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：
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
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Cao, Yunlong;Yisimayi, Ayijiang;Jian, Fanchong;Song, Weiliang;Xiao, Tianhe;Wang, Lei;Du, Shuo;Wang, Jing;Li, Qianqian;Chen, Xiaosu;Yu, Yuanling;Wang, Peng;Zhang, Zhiying;Liu, Pulan;An, Ran;Hao, Xiaohua;Wang, Yao;Feng, Rui;Sun, Haiyan;Zhao, Lijuan;Zhang, Wen;Zhao, Dong;Zheng, Jiang;Yu, Lingling;Li, Can;Zhang, Na;Wang, Rui;Niu, Xiao;Yang, Sijie;Song, Xuetao;Chai, Yangyang;Hu, Ye;Shi, Yansong;Zheng, Linlin;Li, Zhiqiang;Gu, Qingqing;Shao, Fei;Huang, Weijin;Jin, Ronghua;Shen, Zhongyang;Wang, Youchun;Wang, Xiangxi;Xiao, Junyu;Xie, Xiaoliang Sunney
通讯作者：
Xie, Xiaoliang Sunney