Increased resistance of SARS-CoV-2 Omicron variant to neutralization by vaccine-elicited and therapeutic antibodies.
Increased resistance of SARS-CoV-2 Omicron variant to neutralization by vaccine-elicited and therapeutic antibodies.
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DOI：
10.1016/j.ebiom.2022.103944
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发表时间：
2022-04
期刊：
影响因子：
11.1
通讯作者：
Landau, Nathaniel R.
中科院分区：
文献类型：
--
作者：
Tada, Takuya;Zhou, Hao;Dcosta, Belinda M.;Samanovic, Marie I.;Chivukula, Vidya;Herati, Ramin S.;Hubbard, Stevan R.;Mulligan, Mark J.;Landau, Nathaniel R.
目前批准紧急使用的SARS-CoV-2疫苗在预防感染和减轻疾病严重程度方面非常成功。疫苗对早期关注的SARS-CoV-2变体保持有效性，但严重突变、高传染性的Omicron变体对疫苗保护和单克隆抗体治疗都构成障碍。假型慢病毒与接种疫苗和增强供体的血清或治疗性单克隆抗体孵育，然后应用于靶细胞。2天后，用微孔板光度计测定荧光素酶活性。利用点突变的穗蛋白假型鉴定了Omicron穗的抗性突变，并将其映射到三维穗蛋白结构上。携带Omicron刺突蛋白的病毒在两次免疫后对恢复的供体血清中和具有26倍的抗性，对辉瑞BNT162b2和Moderna疫苗诱导的抗体具有26-34倍的抗性。加强免疫增加了对欧米克隆的中和效价。既往有SARS-CoV-2感染史的血清中抗Omicron的中和效价升高。治疗性单克隆抗体分析表明，Regeneron和Eli Lilly单克隆抗体对Omicron假型无效，而Sotrovimab和Evusheld单克隆抗体对Omicron假型部分有效。结果强调了加强免疫的好处，以防止Omicron变异，并证明了单克隆抗体治疗的挑战。对Omicron的中和效价下降表明疫苗的大部分功效可能依赖于T细胞。这项工作由美国国立卫生研究院（NIH）拨款给美国国家研究实验室（DA046100， AI122390和AI120898）和55给M.J.M. （UM1AI148574）资助。
SARS-CoV-2 vaccines currently authorized for emergency use have been highly successful in preventing infection and lessening disease severity. The vaccines maintain effectiveness against earlier SARS-CoV-2 Variants of Concern but the heavily mutated, highly transmissible Omicron variant presents an obstacle both to vaccine protection and monoclonal antibody therapies. Pseudotyped lentiviruses were incubated with serum from vaccinated and boosted donors or therapeutic monoclonal antibody and then applied to target cells. After 2 days, luciferase activity was measured in a microplate luminometer. Resistance mutations of the Omicron spike were identified using point-mutated spike protein pseudotypes and mapped onto the three-dimensional spike protein structure. Virus with the Omicron spike protein was 26-fold resistant to neutralization by recovered donor sera and 26-34-fold resistance to Pfizer BNT162b2 and Moderna vaccine-elicited antibodies following two immunizations. A booster immunization increased neutralizing titres against Omicron. Neutralizing titres against Omicron were increased in the sera with a history of prior SARS-CoV-2 infection. Analysis of the therapeutic monoclonal antibodies showed that the Regeneron and Eli Lilly monoclonal antibodies were ineffective against the Omicron pseudotype while Sotrovimab and Evusheld were partially effective. The results highlight the benefit of a booster immunization to protect against the Omicron variant and demonstrate the challenge to monoclonal antibody therapy. The decrease in neutralizing titres against Omicron suggest that much of the vaccine efficacy may rely on T cells. The work was funded by grants from the NIH to N.R.L. (DA046100, AI122390 and AI120898) and 55 to M.J.M. (UM1AI148574).
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影响因子：
12.8
作者：
Kannan SR;Spratt AN;Sharma K;Chand HS;Byrareddy SN;Singh K
通讯作者：
Singh K
DOI：
10.1056/nejmoa2029849
发表时间：
2021-01-21
期刊：
The New England journal of medicine
影响因子：
--
作者：
Chen P;Nirula A;Heller B;Gottlieb RL;Boscia J;Morris J;Huhn G;Cardona J;Mocherla B;Stosor V;Shawa I;Adams AC;Van Naarden J;Custer KL;Shen L;Durante M;Oakley G;Schade AE;Sabo J;Patel DR;Klekotka P;Skovronsky DM;BLAZE-1 Investigators
通讯作者：
BLAZE-1 Investigators
DOI：
10.1056/nejmoa2102685
发表时间：
2021-10-07
期刊：
The New England journal of medicine
影响因子：
--
作者：
Dougan M;Nirula A;Azizad M;Mocherla B;Gottlieb RL;Chen P;Hebert C;Perry R;Boscia J;Heller B;Morris J;Crystal C;Igbinadolor A;Huhn G;Cardona J;Shawa I;Kumar P;Adams AC;Van Naarden J;Custer KL;Durante M;Oakley G;Schade AE;Holzer TR;Ebert PJ;Higgs RE;Kallewaard NL;Sabo J;Patel DR;Dabora MC;Klekotka P;Shen L;Skovronsky DM;BLAZE-1 Investigators
通讯作者：
BLAZE-1 Investigators
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
DOI：
10.1101/2021.08.09.21261290
发表时间：
2022-01-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gilbert, Peter B;Montefiori, David C;Koup, Richard A
通讯作者：
Koup, Richard A