Reduced sensitivity of the SARS-CoV-2 Lambda variant to monoclonal antibodies and neutralizing antibodies induced by infection and vaccination.
Reduced sensitivity of the SARS-CoV-2 Lambda variant to monoclonal antibodies and neutralizing antibodies induced by infection and vaccination.
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DOI：
10.1080/22221751.2021.2008775
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发表时间：
2022-12
影响因子：
13.2
通讯作者：
Huang W
中科院分区：
文献类型：
--
作者：
Wang M;Zhang L;Li Q;Wang B;Liang Z;Sun Y;Nie J;Wu J;Su X;Qu X;Li Y;Wang Y;Huang W
严重急性呼吸综合征冠状病毒2型变种继续在不同的地理位置出现，具有时间分布。到目前为止，Lambda变种在Spike蛋白中包含多个突变，主要出现在南美洲。该变异体在受体结合域L452Q和F490S上存在两个突变，可能会使其感染性和抗原性改变为中和抗体。在这项研究中，我们构建了10个伪病毒来研究Lambda变异体以及每个氨基酸突变对病毒功能的影响，并使用8个细胞系来研究变异体的感染性。用12份单抗、14份恢复期血清和23份经基因疫苗、灭活疫苗和5型腺病毒载体疫苗免疫的血清研究Lambda变异体的抗原性。我们发现，与D614G参考菌株相比，Lambda对CALU-3和LLC-MK2细胞的感染力分别提高了3.3倍和1.6倍。值得注意的是，Lambda变异体对12种中和单抗9G11、AM180、R126、X593和AbG3中的5种的敏感性显著降低。此外，恢复期和疫苗免疫的血清对Lambda变体的中和滴度平均降低1.3-2.5倍。单突变分析表明，L452Q和F490S突变导致了中和力的降低。总体而言，Lambda变异体的中和能力降低表明，在当前的大流行期间，单抗和疫苗的效力可能会受到影响。
Severe acute respiratory syndrome coronavirus 2 variants have continued to emerge in diverse geographic locations with a temporal distribution. The Lambda variant containing multiple mutations in the spike protein, has thus far appeared mainly in South America. The variant harbours two mutations in the receptor binding domain, L452Q and F490S, which may change its infectivity and antigenicity to neutralizing antibodies. In this study, we constructed 10 pseudoviruses to study the Lambda variant and each individual amino acid mutation's effect on viral function, and used eight cell lines to study variant infectivity. In total, 12 monoclonal antibodies, 14 convalescent sera, and 23 immunized sera induced by mRNA vaccines, inactivated vaccine, and adenovirus type 5 vector vaccine were used to study the antigenicity of the Lambda variant. We found that compared with the D614G reference strain, Lambda demonstrated enhanced infectivity of Calu-3 and LLC-MK2 cells by 3.3-fold and 1.6-fold, respectively. Notably, the sensitivity of the Lambda variant to 5 of 12 neutralizing monoclonal antibodies, 9G11, AM180, R126, X593, and AbG3, was substantially diminished. Furthermore, convalescent- and vaccine-immunized sera showed on average 1.3–2.5-fold lower neutralizing titres against the Lambda variant. Single mutation analysis revealed that this reduction in neutralization was caused by L452Q and F490S mutations. Collectively, the reduced neutralization ability of the Lambda variant suggests that the efficacy of monoclonal antibodies and vaccines may be compromised during the current pandemic.
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DOI：
10.1126/science.abg3055
发表时间：
2021-04-09
期刊：
Science (New York, N.Y.)
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DOI：
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发表时间：
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期刊：
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影响因子：
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