Antigenicity and receptor affinity of SARS-CoV-2 BA.2.86 spike

Qian Wang, Yicheng Guo, Liyuan Liu, Logan T. Schwanz, Zhiteng Li, Manoj S. Nair, Jerren Ho, Richard M. Zhang, Sho Iketani, Jian Yu, Yiming Huang, Yiming Qu, Riccardo Valdez, Adam S. Lauring, Yaoxing Huang, Aubree Gordon, Harris H. Wang, Lihong Liu () and David D. Ho ()
Additional contact information
Qian Wang: Columbia University Vagelos College of Physicians and Surgeons
Yicheng Guo: Columbia University Vagelos College of Physicians and Surgeons
Liyuan Liu: Columbia University Vagelos College of Physicians and Surgeons
Logan T. Schwanz: Columbia University Vagelos College of Physicians and Surgeons
Zhiteng Li: Columbia University Vagelos College of Physicians and Surgeons
Manoj S. Nair: Columbia University Vagelos College of Physicians and Surgeons
Jerren Ho: Columbia University Vagelos College of Physicians and Surgeons
Richard M. Zhang: Columbia University Vagelos College of Physicians and Surgeons
Sho Iketani: Columbia University Vagelos College of Physicians and Surgeons
Jian Yu: Columbia University Vagelos College of Physicians and Surgeons
Yiming Huang: Columbia University Vagelos College of Physicians and Surgeons
Yiming Qu: Columbia University Vagelos College of Physicians and Surgeons
Riccardo Valdez: University of Michigan
Adam S. Lauring: University of Michigan
Yaoxing Huang: Columbia University Vagelos College of Physicians and Surgeons
Aubree Gordon: University of Michigan
Harris H. Wang: Columbia University Vagelos College of Physicians and Surgeons
Lihong Liu: Columbia University Vagelos College of Physicians and Surgeons
David D. Ho: Columbia University Vagelos College of Physicians and Surgeons

Nature, 2023, vol. 624, issue 7992, 639-644

Abstract: Abstract A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant, BA.2.86, has emerged and spread to numerous countries worldwide, raising alarm because its spike protein contains 34 additional mutations compared with its BA.2 predecessor1. We examined its antigenicity using human sera and monoclonal antibodies (mAbs). Reassuringly, BA.2.86 was no more resistant to human sera than the currently dominant XBB.1.5 and EG.5.1, indicating that the new subvariant would not have a growth advantage in this regard. Importantly, sera from people who had XBB breakthrough infection exhibited robust neutralizing activity against all viruses tested, suggesting that upcoming XBB.1.5 monovalent vaccines could confer added protection. Although BA.2.86 showed greater resistance to mAbs to subdomain 1 (SD1) and receptor-binding domain (RBD) class 2 and 3 epitopes, it was more sensitive to mAbs to class 1 and 4/1 epitopes in the ‘inner face’ of the RBD that is exposed only when this domain is in the ‘up’ position. We also identified six new spike mutations that mediate antibody resistance, including E554K that threatens SD1 mAbs in clinical development. The BA.2.86 spike also had a remarkably high receptor affinity. The ultimate trajectory of this new SARS-CoV-2 variant will soon be revealed by continuing surveillance, but its worldwide spread is worrisome.

Date: 2023
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DOI: 10.1038/s41586-023-06750-w

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