Exposure to BA.4/5 S protein drives neutralization of Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5 in vaccine-experienced humans and mice.
Exposure to BA.4/5 S protein drives neutralization of Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5 in vaccine-experienced humans and mice.
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DOI：
10.1126/sciimmunol.ade9888
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发表时间：
2022-12-23
影响因子：
24.8
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中科院分区：
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SARS-CoV-2 Omicron变异体及其亚系由于刺突（S）糖蛋白内超过30个氨基酸的改变而显示出明显的病毒逃避由疫苗接种或先前SARS-CoV-2变异体感染引起的中和抗体。接种Omicron亚系BA.1和BA.2疫苗的个体的突破性感染与针对关注的SARS-CoV-2变体（VOC）的交叉中和活性的不同模式相关。在我们先前工作的延续中，我们表征了Omicron BA.4/BA.5 S糖蛋白暴露对接种个体中突破性感染后中和抗体应答和小鼠中变体适应性加强接种后中和抗体应答的影响。我们发现，在Omicron BA.4/BA.5波期间，来自三重mRNA疫苗接种个体的免疫血清与随后的突破性感染显示出针对先前Omicron变体BA.1、BA.2、BA.2.12.1和BA.4/BA.5本身的交叉中和活性。在SARS-CoV-2野生型毒株基础初次免疫后，向小鼠接种原型BA.4/BA.5适应性mRNA加强疫苗与BA.1适应性加强疫苗相比具有更广泛的交叉中和活性。虽然二价形式（野生型+ BA.1）的Omicron BA-1适应性mRNA疫苗相对于BA.1单价加强疫苗扩大了交叉中和活性，但BA.2和后代的交叉中和在用二价野生型+ BA.4/BA.5疫苗加强的小鼠中更有效。在未处理小鼠中，用二价野生型+ Omicron BA.4/BA.5疫苗初次免疫诱导了针对Omicron VOC和先前变体的强交叉中和活性。这些发现表明，当作为加强剂施用时，单价和二价Omicron BA.4/BA.5适应性疫苗增强了中和宽度，并且二价版本也有可能赋予对SARS-CoV-2没有预先存在的免疫力的个体以保护。来自BA.4/BA.5突破感染个体和BA.4/5加强免疫接种小鼠的免疫血清广泛中和Omicron亚系。
The SARS-CoV-2 Omicron variant and its sublineages show pronounced viral escape from neutralizing antibodies elicited by vaccination or prior SARS-CoV-2 variant infection owing to over 30 amino acid alterations within the spike (S) glycoprotein. Breakthrough infection of vaccinated individuals with Omicron sublineages BA.1 and BA.2 is associated with distinct patterns of cross-neutralizing activity against SARS-CoV-2 variants of concern (VOCs). In continuation of our previous work, we characterized the effect of Omicron BA.4/BA.5 S glycoprotein exposure on the neutralizing antibody response upon breakthrough infection in vaccinated individuals and upon variant-adapted booster vaccination in mice. We found that immune sera from triple mRNA-vaccinated individuals with subsequent breakthrough infection during the Omicron BA.4/BA.5 wave showed cross-neutralizing activity against previous Omicron variants BA.1, BA.2, BA.2.12.1, and BA.4/BA.5 itself. Administration of a prototypic BA.4/BA.5-adapted mRNA booster vaccine to mice following SARS-CoV-2 wild-type strain-based primary immunization is associated with broader cross-neutralizing activity than a BA.1-adapted booster. While the Omicron BA-1-adapted mRNA vaccine in a bivalent format (wild-type + BA.1) broadens cross-neutralizing activity relative to the BA.1 monovalent booster, cross-neutralization of BA.2 and descendants is more effective in mice boosted with a bivalent wild-type + BA.4/BA.5 vaccine. In naïve mice primary immunization with the bivalent wild-type + Omicron BA.4/BA.5 vaccine induces strong cross-neutralizing activity against Omicron VOCs and previous variants. These findings suggest that when administered as boosters, mono- and bivalent Omicron BA.4/BA.5-adapted vaccines enhance neutralization breadth, and that the bivalent version also has the potential to confer protection to individuals with no pre-existing immunity against SARS-CoV-2. Immune sera from BA.4/BA.5 breakthrough infected individuals and BA.4/5 booster-vaccinated mice broadly neutralize Omicron sublineages.
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影响因子：
64.5
作者：
Hoffmann M;Krüger N;Schulz S;Cossmann A;Rocha C;Kempf A;Nehlmeier I;Graichen L;Moldenhauer AS;Winkler MS;Lier M;Dopfer-Jablonka A;Jäck HM;Behrens GMN;Pöhlmann S
通讯作者：
Pöhlmann S
影响因子：
24.8
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影响因子：
24.8
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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
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影响因子：
24.8
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