Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution

Yunlong Cao (), Fanchong Jian, Jing Wang, Yuanling Yu, Weiliang Song, Ayijiang Yisimayi, Jing Wang, Ran An, Xiaosu Chen, Na Zhang, Yao Wang, Peng Wang, Lijuan Zhao, Haiyan Sun, Lingling Yu, Sijie Yang, Xiao Niu, Tianhe Xiao, Qingqing Gu, Fei Shao, Xiaohua Hao, Yanli Xu, Ronghua Jin, Zhongyang Shen, Youchun Wang () and Xiaoliang Sunney Xie ()
Additional contact information
Yunlong Cao: Peking University
Fanchong Jian: Peking University
Jing Wang: Peking University
Yuanling Yu: Changping Laboratory
Weiliang Song: Peking University
Ayijiang Yisimayi: Peking University
Jing Wang: Changping Laboratory
Ran An: Changping Laboratory
Xiaosu Chen: Nankai University
Na Zhang: Changping Laboratory
Yao Wang: Changping Laboratory
Peng Wang: Changping Laboratory
Lijuan Zhao: Changping Laboratory
Haiyan Sun: Changping Laboratory
Lingling Yu: Changping Laboratory
Sijie Yang: Peking University
Xiao Niu: Peking University
Tianhe Xiao: Peking University
Qingqing Gu: Changping Laboratory
Fei Shao: Changping Laboratory
Xiaohua Hao: Capital Medical University
Yanli Xu: Capital Medical University
Ronghua Jin: Capital Medical University
Zhongyang Shen: Nankai University
Youchun Wang: Changping Laboratory
Xiaoliang Sunney Xie: Peking University

Nature, 2023, vol. 614, issue 7948, 521-529

Abstract: Abstract 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 infections2,3. 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 profiles4,5, 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.

Date: 2023
References: Add references at CitEc
Citations: View citations in EconPapers (13)

Downloads: (external link)
https://www.nature.com/articles/s41586-022-05644-7 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:614:y:2023:i:7948:d:10.1038_s41586-022-05644-7

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-022-05644-7

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().