The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution
Open accessAbstract
Continuous evolution of Omicron has led to a rapid and simultaneous emergence of numerous variants that display growth advantages over BA.5 (ref. 1 ). Despite their divergent evolutionary courses, mutations on their receptor-binding domain (RBD) converge on several hotspots. The driving force and destination of such sudden convergent evolution and its effect on humoral immunity remain unclear. Here we demonstrate that these convergent mutations can cause evasion of neutralizing antibody drugs and convalescent plasma, including those from BA.5 breakthrough infection, while maintaining sufficient ACE2-binding capability. BQ.1.1.10 (BQ.1.1 + Y144del), BA.4.6.3, XBB and CH.1.1 are the most antibody-evasive strains tested. To delineate the origin of the convergent evolution, we determined the escape mutation profiles and neutralization activity of monoclonal antibodies isolated from individuals who had BA.2 and BA.5 breakthrough infections 2,3 . Owing to humoral immune imprinting, BA.2 and especially BA.5 breakthrough infection reduced the diversity of the neutralizing antibody binding sites and increased proportions of non-neutralizing antibody clones, which, in turn, focused humoral immune pressure and promoted convergent evolution in the RBD. Moreover, we show that the convergent RBD mutations could be accurately inferred by deep mutational scanning profiles 4,5 , and the evolution trends of BA.2.75 and BA.5 subvariants could be well foreseen through constructed convergent pseudovirus mutants. These results suggest that current herd immunity and BA.5 vaccine boosters may not efficiently prevent the infection of Omicron convergent variants.
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Cites
SARS-CoV-2 variants, spike mutations and immune escape
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Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies
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Self-citationWaning Immune Humoral Response to BNT162b2 Covid-19 Vaccine over 6 Months
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SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies
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Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2
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Potently neutralizing and protective human antibodies against SARS-CoV-2
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Wang, Q., Iketani, S., Li, Z., Liu, L., Guo, Y., Huang, Y., Bowen, A. D., Liu, M., Wang, M., Yu, J., et al. (2023) · Cell · doi:10.1016/j.cell.2022.12.018 · Cited by 912
Guo, Y., Zhang, G., Yang, Q., Xie, X., Lu, Y., Cheng, X., Wang, H., Liang, J., Tang, J., Gao, Y., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-39267-x · Cited by 28
“…recent work has shown that this immunological background can be counterproductive due to immune imprinting or antigen sin, so the antibodies elicited after breakthrough infection remain primarily activated against ancestral strains, leading to poor ef fi cacy against new emerging variants 8,20,21 .”
Self-citationSpoendlin, F. C., Abanades, B., Raybould, M. I. J., Wong, W. K., Georges, G., & Deane, C. M. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2023.1237621 · Cited by 26
SARS-CoV-2 antibodies recognize 23 distinct epitopic sites on the receptor binding domain
Jiang, J., Boughter, C. T., Ahmad, J., Natarajan, K., Boyd, L. F., Meier-Schellersheim, M., & Margulies, D. H. (2023) · Communications Biology · doi:10.1038/s42003-023-05332-w · Cited by 24
A broadly generalizable stabilization strategy for sarbecovirus fusion machinery vaccines
Lee, J., Stewart, C., Schäfer, A., Leaf, E. M., Park, Y.-J., Asarnow, D., Powers, J. M., Treichel, C., Sprouse, K. R., Corti, D., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49656-5 · Cited by 23
Metadata
- Authors
- Cao, Y., Jian, F., Wang, J., Yu, Y., Song, W., Yisimayi, A., Wang, J., An, R., Chen, X., Zhang, N., Wang, Y., Wang, P., Zhao, L., Sun, H., Yu, L., Yang, S., Niu, X., Xiao, T., Gu, Q., Shao, F., Hao, X., Xu, Y., Jin, R., Shen, Z., Wang, Y., & Xie, X. S.
- Venue
- Nature
- Published
- 2022-12-19
- Volume
- 614
- Issue
- 7948
- Pages
- 521-529
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W4312019047
- Cited by
- 841
- References
- 14
- FWCI
- 83.25
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Cao, Y., Jian, F., Wang, J., Yu, Y., Song, W., Yisimayi, A., Wang, J., An, R., Chen, X., Zhang, N., Wang, Y., Wang, P., Zhao, L., Sun, H., Yu, L., Yang, S., Niu, X., Xiao, T., Gu, Q., . . . Xie, X. S. (2023). Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution. Nature. https://doi.org/10.1038/s41586-022-05644-7
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