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Published on: June 14, 2022
Antigenicity and receptor affinity of SARS-CoV-2 BA.2.86 spike
Qian Wang1, Yicheng Guo1, Liyuan Liu2
1Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
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.
Insights
The SARS-CoV-2 Omicron BA.2.86 subvariant shows concerning mutations but similar evasion of human immunity as current variants. XBB breakthrough infection sera may offer protection against BA.2.86.
Area of Science:
- Virology
- Immunology
- Epidemiology
Background:
- A novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant, BA.2.86, has emerged globally.
- BA.2.86 possesses 34 new mutations in its spike protein compared to its BA.2 predecessor, raising concerns about immune evasion.
Purpose of the Study:
- To assess the antigenicity of the SARS-CoV-2 BA.2.86 subvariant.
- To evaluate the effectiveness of human sera and monoclonal antibodies against BA.2.86.
- To determine the potential impact of BA.2.86 on vaccine efficacy.
Main Methods:
- Analysis of BA.2.86 antigenicity using human sera from individuals with varying infection and vaccination histories.
- Testing the neutralization activity of sera against BA.2.86 and other circulating variants (XBB.1.5, EG.5.1).
- Assessing the sensitivity of BA.2.86 to a panel of monoclonal antibodies targeting different spike protein epitopes.
Main Results:
- BA.2.86 demonstrated similar resistance to human sera as currently dominant variants like XBB.1.5 and EG.5.1.
- Sera from individuals with XBB breakthrough infections showed robust neutralizing activity against BA.2.86.
- BA.2.86 exhibited increased resistance to certain monoclonal antibodies targeting subdomain 1 and class 2/3 receptor-binding domain epitopes, but remained sensitive to class 1 and 4/1 epitopes.
- Six new spike mutations, including E554K, were identified as contributing to antibody resistance.
- The BA.2.86 spike protein displayed high receptor binding affinity.
Conclusions:
- The SARS-CoV-2 BA.2.86 subvariant does not appear to possess a significant growth advantage due to immune evasion from existing human sera.
- Upcoming XBB.1.5 monovalent vaccines may provide cross-protection against BA.2.86.
- Specific mutations in BA.2.86 confer resistance to certain monoclonal antibodies, highlighting the need for ongoing surveillance and vaccine development.
- The high receptor affinity and global spread of BA.2.86 warrant continued monitoring.
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