Mary Wilson
Well-known member
Published: September 05, 2022
DOI: https://doi.org/10.1016/j.chom.2022.09.002
Qian Wang, Sho Iketani, Zhiteng Li, Yicheng Guo, Andre Yanchen Yeh, Michael Liu, Jian Yu, Zizhang Sheng, Yaoxing Huang, Lihong Liu, David D. Ho
Highlights
•BA.2.75 is more resistant to neutralization by polyclonal sera than BA.2
•BA.2.75 shows heightened resistance to class 1 and class 3 RBD-directed antibodies
•BA.2.75 is the first variant to show discernible resistance to bebtelovimab
•BA.2.75 exhibits higher human ACE2-binding affinity than other Omicron subvariants
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 to currently circulating BA.2, raising concerns 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 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.
https://www.cell.com/action/showPdf?pii=S1931-3128(22)00419-X
DOI: https://doi.org/10.1016/j.chom.2022.09.002
Qian Wang, Sho Iketani, Zhiteng Li, Yicheng Guo, Andre Yanchen Yeh, Michael Liu, Jian Yu, Zizhang Sheng, Yaoxing Huang, Lihong Liu, David D. Ho
Highlights
•BA.2.75 is more resistant to neutralization by polyclonal sera than BA.2
•BA.2.75 shows heightened resistance to class 1 and class 3 RBD-directed antibodies
•BA.2.75 is the first variant to show discernible resistance to bebtelovimab
•BA.2.75 exhibits higher human ACE2-binding affinity than other Omicron subvariants
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 to currently circulating BA.2, raising concerns 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 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.
https://www.cell.com/action/showPdf?pii=S1931-3128(22)00419-X