SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway.
SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway.
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DOI：
10.1038/s41564-022-01143-7
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发表时间：
2022-08
影响因子：
28.3
通讯作者：
中科院分区：
文献类型：
--
作者：
基于SARS-CoV-2尖峰蛋白的疫苗是应对新冠肺炎的公共卫生反应的基石。高度突变、越来越易传播的关注变异(VOC)的出现威胁到了这一战略。Omicron(B.1.1.529)是第五个被描述的VOC，它在Spike中含有多种氨基酸突变，其中一半位于受体结合区。在这里，我们使用接种了ChAdOx1、BNT162b2和mRNA-1273的个体的血清，在体外证明了Omicron BA.1和BA.2变体对中和的实质性逃避。这些数据反映了现实世界疫苗效力的大幅下降，而加强疫苗接种部分恢复了这一下降。Omicron突变体BA.1和BA.2在体外不能诱导细胞合胞，而是支持TMPRSS2非依赖的内体进入途径，这些表型映射到Spike蛋白的不同区域。受损的细胞融合是由受体结合域确定的，而内体进入映射到S2结构域。这种抗原性和复制生物学上的显著变化可能是奥米克龙变异株在全球迅速传播和改变致病性的基础。Omicron变异体避免了疫苗诱导的中和，但也无法形成合胞体，显示出在人类肺细胞中复制减少，并优先使用TMPRSS2不依赖的细胞进入途径，这可能有助于增强上呼吸道细胞的复制。改变的融合和细胞进入特性与Omicron Spike蛋白的不同区域有关。
Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant. The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.
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CoVID-19疫苗或感染引起的SARS-COV-2 T细胞反应预计将保持对Omicron的稳健性。
DOI：
10.3390/v14010079
发表时间：
2022-01-02
期刊：
Viruses
影响因子：
--
作者：
Ahmed SF;Quadeer AA;McKay MR
通讯作者：
McKay MR
DOI：
10.1056/nejmoa2119451
发表时间：
2022-04-21
期刊：
The New England journal of medicine
影响因子：
--
作者：
Andrews N;Stowe J;Kirsebom F;Toffa S;Rickeard T;Gallagher E;Gower C;Kall M;Groves N;O'Connell AM;Simons D;Blomquist PB;Zaidi A;Nash S;Iwani Binti Abdul Aziz N;Thelwall S;Dabrera G;Myers R;Amirthalingam G;Gharbia S;Barrett JC;Elson R;Ladhani SN;Ferguson N;Zambon M;Campbell CNJ;Brown K;Hopkins S;Chand M;Ramsay M;Lopez Bernal J
通讯作者：
Lopez Bernal J
影响因子：
64.5
作者：
Daniloski Z;Jordan TX;Wessels HH;Hoagland DA;Kasela S;Legut M;Maniatis S;Mimitou EP;Lu L;Geller E;Danziger O;Rosenberg BR;Phatnani H;Smibert P;Lappalainen T;tenOever BR;Sanjana NE
通讯作者：
Sanjana NE
具有不同SARBECOVIRUS受体结合结构域的免疫接种引起了SARS-COV-2中和抗体，以抵抗保守的脆弱性位点。
影响因子：
32.4
作者：
Burnett DL;Jackson KJL;Langley DB;Aggrawal A;Stella AO;Johansen MD;Balachandran H;Lenthall H;Rouet R;Walker G;Saunders BM;Singh M;Li H;Henry JY;Jackson J;Stewart AG;Witthauer F;Spence MA;Hansbro NG;Jackson C;Schofield P;Milthorpe C;Martinello M;Schulz SR;Roth E;Kelleher A;Emery S;Britton WJ;Rawlinson WD;Karl R;Schäfer S;Winkler TH;Brink R;Bull RA;Hansbro PM;Jäck HM;Turville S;Christ D;Goodnow CC
通讯作者：
Goodnow CC
影响因子：
64.8
作者：
Cho A;Muecksch F;Schaefer-Babajew D;Wang Z;Finkin S;Gaebler C;Ramos V;Cipolla M;Mendoza P;Agudelo M;Bednarski E;DaSilva J;Shimeliovich I;Dizon J;Daga M;Millard KG;Turroja M;Schmidt F;Zhang F;Tanfous TB;Jankovic M;Oliveria TY;Gazumyan A;Caskey M;Bieniasz PD;Hatziioannou T;Nussenzweig MC
通讯作者：
Nussenzweig MC