Rapid escape of new SARS-CoV-2 Omicron variants from BA.2-directed antibody responses.
Rapid escape of new SARS-CoV-2 Omicron variants from BA.2-directed antibody responses.
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DOI：
10.1016/j.celrep.2023.112271
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发表时间：
2023-04-25
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
2021年11月，含有大量新刺突突变的Omicron BA.1出现并迅速在全球传播。为了逃避疫苗或严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）感染所产生的抗体反应，巨大的选择压力导致了欧米克隆亚系的快速连续，先是BA.2，然后是BA.4/5感染。最近出现了许多变异，如bq1和XBB，与BA.2相比，它们携带多达8个额外的受体结合域（RBD）氨基酸取代。我们描述了一组25强效单克隆抗体（mab），这些单克隆抗体是由遭受BA.2突破性感染的疫苗产生的。表位定位显示单抗结合转移到3个簇，其中2个对应于大流行早期的结合热点。最近变异的RBD突变位于这些结合位点附近，敲除或严重敲除除1个有效单抗外的所有单抗的中和活性。最近的单抗逃逸与疫苗或BA.1、BA.2或BA.4/5免疫血清的中和效价大幅下降相对应。Dijokaite-Guraliuc等人分析了BA.2突破性感染疫苗接种者产生的25种强效RBD单克隆抗体。强效单克隆抗体结合3个簇，2个簇对应于大流行早期的结合热点。最近变体中的RBD突变与这些结合位点接近，除1个外，其余单克隆抗体的中和活性均降低。抗体结合受体结合域上的3个位点，其中2个与早期大流行抗体相同。最近的突变与这些位点密切相关，导致除一个单抗外所有单抗的中和作用减少。
In November 2021, Omicron BA.1, containing a raft of new spike mutations, emerged and quickly spread globally. Intense selection pressure to escape the antibody response produced by vaccines or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection then led to a rapid succession of Omicron sub-lineages with waves of BA.2 and then BA.4/5 infection. Recently, many variants have emerged such as BQ.1 and XBB, which carry up to 8 additional receptor-binding domain (RBD) amino acid substitutions compared with BA.2. We describe a panel of 25 potent monoclonal antibodies (mAbs) generated from vaccinees suffering BA.2 breakthrough infections. Epitope mapping shows potent mAb binding shifting to 3 clusters, 2 corresponding to early-pandemic binding hotspots. The RBD mutations in recent variants map close to these binding sites and knock out or severely knock down neutralization activity of all but 1 potent mAb. This recent mAb escape corresponds with large falls in neutralization titer of vaccine or BA.1, BA.2, or BA.4/5 immune serum. 25 potent RBD mAbs generated from vaccinees suffering BA.2 breakthrough infections Potent mAbs bind 3 clusters, 2 correspond to early-pandemic binding hotspots RBD mutations in recent variants map close to these binding sites Neutralization activity of all but 1 potent mAb is reduced Dijokaite-Guraliuc et al. analyze potently neutralizing antibodies from vaccinated individuals with BA.2 breakthrough infections. The antibodies bind 3 sites on the receptor-binding domain, 2 of which are in common with early-pandemic antibodies. Mutations in more recent variants map closely to these sites, leading to reduced neutralization in all but one mAb.
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影响因子：
64.5
作者：
Nutalai, Rungtiwa;Zhou, Daming;Tuekprakhon, Aekkachai;Ginn, Helen M.;Supasa, Piyada;Liu, Chang;Huo, Jiandong;Mentzer, Alexander J.;Duyvesteyn, Helen M. E.;Dijokaite-Guraliuc, Aiste;Skelly, Donal;Ritter, Thomas G.;Amini, Ali;Bibi, Sagida;Adele, Sandra;Johnson, Sile Ann;Constantinides, Bede;Webster, Hermione;Temperton, Nigel;Klenerman, Paul;Barnes, Eleanor;Dunachie, Susanna J.;Crook, Derrick;Pollard, Andrew J.;Lambe, Teresa;Goulder, Philip;Paterson, Neil G.;Williams, Mark A.;Hall, David R.;Mongkolsapaya, Juthathip;Fry, Elizabeth E.;Dejnirattisai, Wanwisa;Ren, Jingshan;Stuart, David, I;Screaton, Gavin R.
通讯作者：
Screaton, Gavin R.
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
影响因子：
56.9
作者：
McCallum, Matthew;Czudnochowski, Nadine;Rosen, Laura E.;Zepeda, Samantha K.;Bowen, John E.;Walls, Alexandra C.;Hauser, Kevin;Joshi, Anshu;Stewart, Cameron;Dillen, Josh R.;Powell, Abigail E.;Croll, Tristan, I;Nix, Jay;Virgin, Herbert W.;Corti, Davide;Snell, Gyorgy;Veesler, David
通讯作者：
Veesler, David
影响因子：
64.5
作者：
Liu C;Ginn HM;Dejnirattisai W;Supasa P;Wang B;Tuekprakhon A;Nutalai R;Zhou D;Mentzer AJ;Zhao Y;Duyvesteyn HME;López-Camacho C;Slon-Campos J;Walter TS;Skelly D;Johnson SA;Ritter TG;Mason C;Costa Clemens SA;Gomes Naveca F;Nascimento V;Nascimento F;Fernandes da Costa C;Resende PC;Pauvolid-Correa A;Siqueira MM;Dold C;Temperton N;Dong T;Pollard AJ;Knight JC;Crook D;Lambe T;Clutterbuck E;Bibi S;Flaxman A;Bittaye M;Belij-Rammerstorfer S;Gilbert SC;Malik T;Carroll MW;Klenerman P;Barnes E;Dunachie SJ;Baillie V;Serafin N;Ditse Z;Da Silva K;Paterson NG;Williams MA;Hall DR;Madhi S;Nunes MC;Goulder P;Fry EE;Mongkolsapaya J;Ren J;Stuart DI;Screaton GR
通讯作者：
Screaton GR