[PDF][PDF] Antigenic characterization of the SARS-CoV-2 Omicron subvariant BA. 2.75

Q Wang, S Iketani, Z Li, Y Guo, AY Yeh, M Liu, J Yu… - Cell host & …, 2022 - cell.com
Q Wang, S Iketani, Z Li, Y Guo, AY Yeh, M Liu, J Yu, Z Sheng, Y Huang, L Liu, DD Ho
Cell host & microbe, 2022cell.com
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant
BA. 2.75 emerged recently and appears to be spreading. It has nine mutations in spike
compared with the currently circulating BA. 2, raising concerns that it may further evade
vaccine-elicited and therapeutic antibodies. We found BA. 2.75 to be moderately more
neutralization resistant to sera from vaccinated/boosted individuals than BA. 2 (1.8-fold),
similar to BA. 2.12. 1 (1.1-fold), but more neutralization sensitive than BA. 4/5 (0.6-fold) …
Summary
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant BA.2.75 emerged recently and appears to be spreading. It has nine mutations in spike compared with the currently circulating BA.2, raising concerns that it may further evade vaccine-elicited and therapeutic antibodies. We found BA.2.75 to be moderately more neutralization resistant to sera from vaccinated/boosted individuals than BA.2 (1.8-fold), similar to BA.2.12.1 (1.1-fold), but more neutralization sensitive than BA.4/5 (0.6-fold). Relative to BA.2, BA.2.75 showed heightened resistance to class 1 and class 3 monoclonal antibodies targeting the spike-receptor-binding domain while gaining sensitivity to class 2 antibodies. Resistance was largely conferred by G446S and R460K mutations. BA.2.75 was slightly resistant (3.7-fold) to bebtelovimab, a therapeutic antibody with potent activity against all Omicron subvariants. BA.2.75 also exhibited a higher binding affinity to host receptor ACE2 than other Omicron subvariants. BA.2.75 provides further insight into SARS-CoV-2 evolution as it gains transmissibility while incrementally evading antibody neutralization.
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