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Reduced sensitivity of the SARS-CoV-2 Lambda variant to monoclonal antibodies and neutralizing antibodies induced by infection and vaccination.
Emerg Microbes Infect. 2022 Dec; 11(1):18-29.EM

Abstract

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.

Authors+Show Affiliations

Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing, People's Republic of China. Graduate School of Peking Union Medical College, Beijing, People's Republic of China.Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing, People's Republic of China.Jiangsu Recbio Technology Co., Ltd., Taizhou, People's Republic of China.Beijing Advanced Innovation Center for Genomics (ICG) & Biomedical Pioneering Innovation Center (BIOPIC), Peking University; State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, People's Republic of China.Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing, People's Republic of China. Graduate School of Peking Union Medical College, Beijing, People's Republic of China.Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing, People's Republic of China.Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing, People's Republic of China.Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing, People's Republic of China.Beijing Advanced Innovation Center for Genomics (ICG) & Biomedical Pioneering Innovation Center (BIOPIC), Peking University; State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, People's Republic of China.Translational Medicine Institute, The First People's Hospital of Chenzhou, University of South China, Chenzhou, People's Republic of China.Department of Arboviral Vaccine, National Institutes for Food and Drug Control, Beijing, People's Republic of China.Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing, People's Republic of China. Graduate School of Peking Union Medical College, Beijing, People's Republic of China.Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing, People's Republic of China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

34818119

Citation

Wang, Meiyu, et al. "Reduced Sensitivity of the SARS-CoV-2 Lambda Variant to Monoclonal Antibodies and Neutralizing Antibodies Induced By Infection and Vaccination." Emerging Microbes & Infections, vol. 11, no. 1, 2022, pp. 18-29.
Wang M, Zhang L, Li Q, et al. Reduced sensitivity of the SARS-CoV-2 Lambda variant to monoclonal antibodies and neutralizing antibodies induced by infection and vaccination. Emerg Microbes Infect. 2022;11(1):18-29.
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. (2022). Reduced sensitivity of the SARS-CoV-2 Lambda variant to monoclonal antibodies and neutralizing antibodies induced by infection and vaccination. Emerging Microbes & Infections, 11(1), 18-29. https://doi.org/10.1080/22221751.2021.2008775
Wang M, et al. Reduced Sensitivity of the SARS-CoV-2 Lambda Variant to Monoclonal Antibodies and Neutralizing Antibodies Induced By Infection and Vaccination. Emerg Microbes Infect. 2022;11(1):18-29. PubMed PMID: 34818119.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduced sensitivity of the SARS-CoV-2 Lambda variant to monoclonal antibodies and neutralizing antibodies induced by infection and vaccination. AU - Wang,Meiyu, AU - Zhang,Li, AU - Li,Qianqian, AU - Wang,Bo, AU - Liang,Ziteng, AU - Sun,Yeqing, AU - Nie,Jianhui, AU - Wu,Jiajing, AU - Su,Xiaodong, AU - Qu,Xiaowang, AU - Li,Yuhua, AU - Wang,Youchun, AU - Huang,Weijin, PY - 2021/11/25/pubmed PY - 2022/1/1/medline PY - 2021/11/24/entrez KW - C.37 KW - Lambda variant KW - SARS-CoV-2 KW - convalescent serum KW - monoclonal antibodies KW - neutralization KW - vaccines SP - 18 EP - 29 JF - Emerging microbes & infections JO - Emerg Microbes Infect VL - 11 IS - 1 N2 - 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. SN - 2222-1751 UR - https://www.unboundmedicine.com/medline/citation/34818119/Reduced_sensitivity_of_the_SARS_CoV_2_Lambda_variant_to_monoclonal_antibodies_and_neutralizing_antibodies_induced_by_infection_and_vaccination_ L2 - https://www.tandfonline.com/doi/full/10.1080/22221751.2021.2008775 DB - PRIME DP - Unbound Medicine ER -