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SARS-CoV-2 evolves to reduce but not abolish neutralizing action.
J Med Virol. 2023 01; 95(1):e28207.JM

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) have prolonged coronavirus disease 2019 (COVID-19) pandemic by escaping pre-existing immunity acquired by natural infection or vaccination. Elucidation of VOCs' mutation trends and evasion of neutralization is required to update current control measures. Mutations and the prevalence of VOCs were analyzed in the global immunization coverage rate context. Lentivirus-based pseudovirus neutralization analysis platforms for SARS-CoV-2 prototype strain (PS) and VOCs, containing Alpha, Beta, Gamma, Delta, and Omicron, were constructed based on the spike protein of each variant and HEK 293T cell line expressing the human angiotensin-converting enzyme 2 (hACE2) receptor on the surface, and an enhanced green fluorescent protein reporter. Serum samples from 65 convalescent individuals and 20 WIBP-CorV vaccine recipients and four therapeutic monoclonal antibodies (mAbs) namely imdevimab, casirivimab, bamlanivimab, and etesevimab were used to evaluate the neutralization potency against the variants. Pseudovirus-based neutralization assay platforms for PS and VOCs were established, and multiplicity of infection (MOI) was the key factor influencing the assay result. Compared to PS, VOCs may enhance the infectivity of hACE2-293T cells. Except for Alpha, other VOCs escaped neutralization to varying degrees. Attributed to favorable and emerging mutations, the current pandemic Omicron variant of all VOCs demonstrated the most significant neutralization-escaping ability to the sera and mAbs. Compared with the PS pseudovirus, Omicron had 15.7- and 3.71-fold decreases in the NT50 value (the highest serum dilution corresponding to a neutralization rate of 50%); and correspondingly, 90% and 43% of immunization or convalescent serum samples lost their neutralizing activity against the Omicron variant, respectively. Therefore, SARS-CoV-2 has evolved persistently with a strong ability to escape neutralization and prevailing against the established immune barrier. Our findings provide important clues to controlling the COVID-19 pandemic caused by new variants.

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Authors+Show Affiliations

Zhang Y
Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Ndzouboukou JB
Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Lin X
Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Hou H
Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Wang F
Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yuan L
Department of Clinical Laboratory, Southern University of Science and Technology Hospital, Shenzhen, China.
Gan M
Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yao Z
Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Fu H
Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Cao J
Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Fan X
Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

MeSH

HumansSARS-CoV-2COVID-19COVID-19 SerotherapyPandemicsAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralSpike Glycoprotein, Coronavirus

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

36217880

Citation

Zhang, Yandi, et al. "SARS-CoV-2 Evolves to Reduce but Not Abolish Neutralizing Action." Journal of Medical Virology, vol. 95, no. 1, 2023, pp. e28207.
Zhang Y, Ndzouboukou JB, Lin X, et al. SARS-CoV-2 evolves to reduce but not abolish neutralizing action. J Med Virol. 2023;95(1):e28207.
Zhang, Y., Ndzouboukou, J. B., Lin, X., Hou, H., Wang, F., Yuan, L., Gan, M., Yao, Z., Fu, H., Cao, J., & Fan, X. (2023). SARS-CoV-2 evolves to reduce but not abolish neutralizing action. Journal of Medical Virology, 95(1), e28207. https://doi.org/10.1002/jmv.28207
Zhang Y, et al. SARS-CoV-2 Evolves to Reduce but Not Abolish Neutralizing Action. J Med Virol. 2023;95(1):e28207. PubMed PMID: 36217880.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SARS-CoV-2 evolves to reduce but not abolish neutralizing action. AU - Zhang,Yandi, AU - Ndzouboukou,Jo-Lewis B, AU - Lin,Xiaosong, AU - Hou,Hongyan, AU - Wang,Feng, AU - Yuan,Leyong, AU - Gan,Mengze, AU - Yao,Zongjie, AU - Fu,Hui, AU - Cao,Jinge, AU - Fan,Xionglin, Y1 - 2022/10/19/ PY - 2022/09/25/revised PY - 2022/08/29/received PY - 2022/10/02/accepted PY - 2022/10/12/pubmed PY - 2023/1/11/medline PY - 2022/10/11/entrez KW - COVID-19 KW - SARS-CoV-2 KW - VOCs KW - immune escape KW - neutralizing antibodies SP - e28207 EP - e28207 JF - Journal of medical virology JO - J Med Virol VL - 95 IS - 1 N2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) have prolonged coronavirus disease 2019 (COVID-19) pandemic by escaping pre-existing immunity acquired by natural infection or vaccination. Elucidation of VOCs' mutation trends and evasion of neutralization is required to update current control measures. Mutations and the prevalence of VOCs were analyzed in the global immunization coverage rate context. Lentivirus-based pseudovirus neutralization analysis platforms for SARS-CoV-2 prototype strain (PS) and VOCs, containing Alpha, Beta, Gamma, Delta, and Omicron, were constructed based on the spike protein of each variant and HEK 293T cell line expressing the human angiotensin-converting enzyme 2 (hACE2) receptor on the surface, and an enhanced green fluorescent protein reporter. Serum samples from 65 convalescent individuals and 20 WIBP-CorV vaccine recipients and four therapeutic monoclonal antibodies (mAbs) namely imdevimab, casirivimab, bamlanivimab, and etesevimab were used to evaluate the neutralization potency against the variants. Pseudovirus-based neutralization assay platforms for PS and VOCs were established, and multiplicity of infection (MOI) was the key factor influencing the assay result. Compared to PS, VOCs may enhance the infectivity of hACE2-293T cells. Except for Alpha, other VOCs escaped neutralization to varying degrees. Attributed to favorable and emerging mutations, the current pandemic Omicron variant of all VOCs demonstrated the most significant neutralization-escaping ability to the sera and mAbs. Compared with the PS pseudovirus, Omicron had 15.7- and 3.71-fold decreases in the NT50 value (the highest serum dilution corresponding to a neutralization rate of 50%); and correspondingly, 90% and 43% of immunization or convalescent serum samples lost their neutralizing activity against the Omicron variant, respectively. Therefore, SARS-CoV-2 has evolved persistently with a strong ability to escape neutralization and prevailing against the established immune barrier. Our findings provide important clues to controlling the COVID-19 pandemic caused by new variants. SN - 1096-9071 UR - https://www.unboundmedicine.com/medline/citation/36217880/SARS_CoV_2_evolves_to_reduce_but_not_abolish_neutralizing_action_ DB - PRIME DP - Unbound Medicine ER -