Enhanced evasion of neutralizing antibody response by Omicron XBB.1.5, CH.1.1, and CA.3.1 variants.
Enhanced evasion of neutralizing antibody response by Omicron XBB.1.5, CH.1.1, and CA.3.1 variants.
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DOI：
10.1016/j.celrep.2023.112443
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发表时间：
2023-05-30
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
Omicron亚变体不断挑战当前的疫苗接种策略。在这里，我们证明了XBB.1.5，CH.1.1和CA.3.1变体几乎完全逃脱由三剂mRNA疫苗或BA.4/5波感染刺激的中和抗体，但中和被含BA.5的二价加强剂拯救。CH.1.1和CA.3.1显示出对单克隆抗体S309的强免疫逃逸。此外，XBB.1.5、CH.1.1和CA.3.1刺突蛋白与BA.2相比，融合性增加，加工增强。同源性建模揭示了G252 V和F486 P在XBB.1.5的中和抗性中的关键作用，其中F486 P还增强受体结合。此外，CH. 1.1和CA. 3.1中的K444 T/M和L452 R可能驱动II类中和抗体的逃逸，而R346 T和G339 H突变可赋予这两种亚变体对S309样抗体的强中和抗性。总体而言，我们的结果支持需要给予二价mRNA疫苗和继续监测Omicron亚变体。Qu等人表明，与单价受体相比，二价加强受体表现出更高的针对Omicron亚变体XBB、XBB.1和XBB.1.5的nAb滴度。CH. 1.1和CA. 3.1变体显示出比XBB变体更显著的中和逃逸。此外，结构建模揭示了XBB.1.5中的F486 P突变增强了ACE 2结合。
Omicron subvariants continuingly challenge current vaccination strategies. Here, we demonstrate nearly complete escape of the XBB.1.5, CH.1.1, and CA.3.1 variants from neutralizing antibodies stimulated by three doses of mRNA vaccine or by BA.4/5 wave infection, but neutralization is rescued by a BA.5-containing bivalent booster. CH.1.1 and CA.3.1 show strong immune escape from monoclonal antibody S309. Additionally, XBB.1.5, CH.1.1, and CA.3.1 spike proteins exhibit increased fusogenicity and enhanced processing compared with BA.2. Homology modeling reveals the key roles of G252V and F486P in the neutralization resistance of XBB.1.5, with F486P also enhancing receptor binding. Further, K444T/M and L452R in CH.1.1 and CA.3.1 likely drive escape from class II neutralizing antibodies, whereas R346T and G339H mutations could confer the strong neutralization resistance of these two subvariants to S309-like antibodies. Overall, our results support the need for administration of the bivalent mRNA vaccine and continued surveillance of Omicron subvariants. Qu et al. show that bivalent booster recipients, compared with monovalent recipients, exhibit higher nAb titers against Omicron subvariants XBB, XBB.1, and XBB.1.5. The CH.1.1 and CA.3.1 variants show more substantial neutralization escape than the XBB variants. Further, structural modeling reveals that the F486P mutation in XBB.1.5 enhances ACE2 binding.
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影响因子：
30.3
作者：
Arora, Prerna;Zhang, Lu;Krueger, Nadine;Rocha, Cheila;Sidarovich, Anzhalika;Schulz, Sebastian;Kempf, Amy;Graichen, Luise;Moldenhauer, Anna-Sophie;Cossmann, Anne;Dopfer-Jablonka, Alexandra;Behrens, Georg M. N.;Jaeck, Hans-Martin;Poehlmann, Stefan;Hoffmann, Markus
通讯作者：
Hoffmann, Markus
影响因子：
30.3
作者：
Qu, Panke;Evans, John P.;Faraone, Julia N.;Zheng, Yi-Min;Carlin, Claire;Anghelina, Mirela;Stevens, Patrick;Fernandez, Soledad;Jones, Daniel;Lozanski, Gerard;Panchal, Ashish;Saif, Linda J.;Oltz, Eugene M.;Xu, Kai;Gumina, Richard J.;Liu, Shan-Lu
通讯作者：
Liu, Shan-Lu
影响因子：
30.3
作者：
Evans, John P.;Zeng, Cong;Qu, Panke;Faraone, Julia;Zheng, Yi-Min;Carlin, Claire;Bednash, Joseph S.;Zhou, Tongqing;Lozanski, Gerard;Mallampalli, Rama;Saif, Linda J.;Oltz, Eugene M.;Mohler, Peter J.;Xu, Kai;Gumina, Richard J.;Liu, Shan-Lu
通讯作者：
Liu, Shan-Lu
影响因子：
64.8
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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
影响因子：
64.8
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Meng B;Abdullahi A;Ferreira IATM;Goonawardane N;Saito A;Kimura I;Yamasoba D;Gerber PP;Fatihi S;Rathore S;Zepeda SK;Papa G;Kemp SA;Ikeda T;Toyoda M;Tan TS;Kuramochi J;Mitsunaga S;Ueno T;Shirakawa K;Takaori-Kondo A;Brevini T;Mallery DL;Charles OJ;CITIID-NIHR BioResource COVID-19 Collaboration;Genotype to Phenotype Japan (G2P-Japan) Consortium;Ecuador-COVID19 Consortium;Bowen JE;Joshi A;Walls AC;Jackson L;Martin D;Smith KGC;Bradley J;Briggs JAG;Choi J;Madissoon E;Meyer KB;Mlcochova P;Ceron-Gutierrez L;Doffinger R;Teichmann SA;Fisher AJ;Pizzuto MS;de Marco A;Corti D;Hosmillo M;Lee JH;James LC;Thukral L;Veesler D;Sigal A;Sampaziotis F;Goodfellow IG;Matheson NJ;Sato K;Gupta RK
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Gupta RK