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Cross-reactivity of eight SARS-CoV-2 variants rationally predicts immunogenicity clustering in sarbecoviruses.

Qianqian LiLi ZhangZiteng LiangNan WangShuo LiuTao LiYuanling YuQianqian CuiXi WuJianhui NieJiajing WuZhimin CuiQiong LuXiangxi WangWei Jin HuangYou-Chun Wang
Published in: Signal transduction and targeted therapy (2022)
A steep rise in Omicron reinfection cases suggests that this variant has increased immune evasion ability. To evaluate its antigenicity relationship with other variants, antisera from guinea pigs immunized with spike protein of SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs) were cross-tested against pseudotyped variants. The neutralization activity against Omicron was markedly reduced when other VOCs or VOIs were used as immunogens, and Omicron (BA.1)-elicited sera did not efficiently neutralize the other variants. However, a Beta or Omicron booster, when administered as the 4th dose 3-months after the 3rd dose of any of the variants, could elicit broad neutralizing antibodies against all of the current variants including Omicron BA.1. Further analysis with 280 available antigen-antibody structures and quantification of immune escape from 715 reported neutralizing antibodies provide explanations for the observed differential immunogenicity. Three distinct clades predicted using an in silico algorithm for clustering of sarbecoviruses based on immune escape provide key information for rational design of vaccines.
Keyphrases
  • copy number
  • sars cov
  • machine learning
  • healthcare
  • dna methylation
  • genome wide
  • deep learning
  • respiratory syndrome coronavirus
  • small molecule
  • protein protein