Antibody evasion by SARS-CoV-2 Omicron subvariants BA.2.12.1, BA.4 and BA.5

Qian Wang, Yicheng Guo, Sho Iketani, Manoj S. Nair, Zhiteng Li, Hiroshi Mohri, Maple Wang, Jian Yu, Anthony D. Bowen, Jennifer Y. Chang, Jayesh G. Shah, Nadia Nguyen, Zhiwei Chen, Kathrine Meyers, Michael T. Yin, Magdalena E. Sobieszczyk, Zizhang Sheng, Yaoxing Huang, 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
Sho Iketani: Columbia University Vagelos College of Physicians and Surgeons
Manoj S. Nair: Columbia University Vagelos College of Physicians and Surgeons
Zhiteng Li: Columbia University Vagelos College of Physicians and Surgeons
Hiroshi Mohri: Columbia University Vagelos College of Physicians and Surgeons
Maple Wang: Columbia University Vagelos College of Physicians and Surgeons
Jian Yu: Columbia University Vagelos College of Physicians and Surgeons
Anthony D. Bowen: Columbia University Vagelos College of Physicians and Surgeons
Jennifer Y. Chang: Columbia University Vagelos College of Physicians and Surgeons
Jayesh G. Shah: Columbia University Vagelos College of Physicians and Surgeons
Nadia Nguyen: Columbia University Vagelos College of Physicians and Surgeons
Zhiwei Chen: The University of Hong Kong
Kathrine Meyers: Columbia University Vagelos College of Physicians and Surgeons
Michael T. Yin: Columbia University Vagelos College of Physicians and Surgeons
Magdalena E. Sobieszczyk: Columbia University Vagelos College of Physicians and Surgeons
Zizhang Sheng: Columbia University Vagelos College of Physicians and Surgeons
Yaoxing Huang: 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, 2022, vol. 608, issue 7923, 603-608

Abstract: Abstract SARS-CoV-2 Omicron subvariants BA.2.12.1 and BA.4/5 have surged notably to become dominant in the United States and South Africa, respectively1,2. These new subvariants carrying further mutations in their spike proteins raise concerns that they may further evade neutralizing antibodies, thereby further compromising the efficacy of COVID-19 vaccines and therapeutic monoclonals. We now report findings from a systematic antigenic analysis of these surging Omicron subvariants. BA.2.12.1 is only modestly (1.8-fold) more resistant to sera from vaccinated and boosted individuals than BA.2. However, BA.4/5 is substantially (4.2-fold) more resistant and thus more likely to lead to vaccine breakthrough infections. Mutation at spike residue L452 found in both BA.2.12.1 and BA.4/5 facilitates escape from some antibodies directed to the so-called class 2 and 3 regions of the receptor-binding domain3. The F486V mutation found in BA.4/5 facilitates escape from certain class 1 and 2 antibodies but compromises the spike affinity for the viral receptor. The R493Q reversion mutation, however, restores receptor affinity and consequently the fitness of BA.4/5. Among therapeutic antibodies authorized for clinical use, only bebtelovimab retains full potency against both BA.2.12.1 and BA.4/5. The Omicron lineage of SARS-CoV-2 continues to evolve, successively yielding subvariants that are not only more transmissible but also more evasive to antibodies.

Date: 2022
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DOI: 10.1038/s41586-022-05053-w

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