SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion.

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion.
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DOI:
10.1038/s41586-021-03944-y
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发表时间:
2021-11
期刊:
影响因子:
64.8
通讯作者:
Gupta RK
Gupta RK
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Mlcochova P;Kemp SA;Dhar MS;Papa G;Meng B;Ferreira IATM;Datir R;Collier DA;Albecka A;Singh S;Pandey R;Brown J;Zhou J;Goonawardane N;Mishra S;Whittaker C;Mellan T;Marwal R;Datta M;Sengupta S;Ponnusamy K;Radhakrishnan VS;Abdullahi A;Charles O;Chattopadhyay P;Devi P;Caputo D;Peacock T;Wattal C;Goel N;Satwik A;Vaishya R;Agarwal M;Indian SARS-CoV-2 Genomics Consortium (INSACOG);Genotype to Phenotype Japan (G2P-Japan) Consortium;CITIID-NIHR BioResource COVID-19 Collaboration;Mavousian A;Lee JH;Bassi J;Silacci-Fegni C;Saliba C;Pinto D;Irie T;Yoshida I;Hamilton WL;Sato K;Bhatt S;Flaxman S;James LC;Corti D;Piccoli L;Barclay WS;Rakshit P;Agrawal A;Gupta RK

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严重急性呼吸系统综合征冠状病毒2型(SARS-CoV-2)的B.1.617.2(Delta)变体于2020年底首次在马哈拉施特拉邦被发现,并在整个印度传播,击败了包括B.1.617.1(Kappa)和B.1.1.7(Alpha)在内的先前存在的谱系。在体外,与携带D 614 G的野生型Wuhan-1相比,B.1.617.2对来自恢复个体的血清中和抗体的敏感性低6倍,对疫苗引起的抗体的敏感性低8倍。ChAdOx 1疫苗接种者中抗B.1.617.2的血清中和滴度低于BNT 162 b2疫苗接种者。B.1.617.2刺突假型病毒对受体结合结构域和氨基末端结构域的单克隆抗体的敏感性降低。在气道类器官和人气道上皮系统中,B.1.617.2的复制效率均高于B.1.1.7,这与B.1.1.7加标相比,B.1.617.2加标处于主要裂解状态有关。与野生型刺突蛋白相比,B.1.617.2刺突蛋白能够介导对中和抗体的抑制不太敏感的高效合胞体形成。我们还观察到B.1.617.2比B.1.617.1具有更高的复制和尖峰介导的进入,这可能解释了B.1.617.2的优势。在对印度三个中心的130多名SARS-CoV-2感染的卫生保健工作者在混合谱系循环期间进行的分析中,我们观察到ChAdOx 1疫苗对B.1.617.2的有效性相对于非B.1.617.2有所降低,并警告可能存在残留混淆。针对高度契合和免疫逃避的B.1.617.2 Delta变体的疫苗效力受损,需要在疫苗接种后继续采取感染控制措施。一项关于SARS-CoV-2变异体的研究检查了它们的传播,传染性和对治疗的潜在抗性,为Delta变异体的生物学及其在全球大流行中的作用提供了见解。
The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha). In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era. A study of SARS-CoV-2 variants examining their transmission, infectivity, and potential resistance to therapies provides insights into the biology of the Delta variant and its role in the global pandemic.
DOI: 10.1093/infdis/jiab368
发表时间: 2021-09-17
期刊: The Journal of infectious diseases
影响因子: --
作者:
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通讯作者: Genotype to Phenotype Japan (G2P-Japan) Consortium
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DOI: 10.1371/journal.ppat.1009246
发表时间: 2021-01
期刊: PLoS pathogens
影响因子: 6.7
作者:
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发表时间: 2021-06-29
期刊: Cell reports
影响因子: 8.8
作者:
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DOI: 10.1371/journal.pone.0247115
发表时间: 2021
期刊: PloS one
影响因子: 3.7
作者:
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影响因子: 10.7
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