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HIGH-THROUGHPUT DEEP MUTATIONAL SCANNING (DMS) FOR PREDICTING SARS-COV-2 IMMUNE ESCAPE MUTATIONS

2023-01-18

  •   A world-leading platform for SARS-CoV-2 antibody/ vaccine studies was set up, allowing fast measurement of the immune pressure induced by infection and vaccination.

  •  Capability of quickly assessing the efficacy of established antibody drugs and population immunity against newly emgered variants.

  •  Escape mutation profiles of over 6,000 SARS-CoV-2 antibodies were obtained, enabling us to predict which mutations and variants are the most likely to circulate.

  •  Reveal and rationalize the phenomenon of“convergent evolution” of SARS-CoV-2 Omicron receptor-binding domain (RBD).



MACS-based high-throughput yeast display mutation screening

High-throughput escape-mutations profiling and epitope classification of Nabs


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Deciphering humoral immune responses to SARS-CoV-2

Omicron breakthrough infection is limited by immune imprinting


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  • Revealing the humoral immune escape mechanisms of Omicron subvariants: Omicron BA.1 could render most NAb drugs ineffective and cause a substantial reduction in vaccine-induced neutralization titers.

  • Prospectively alerted the global prevalence of BA.4/5 and BA.2.75: BA.4/BA.5 can escape antibodies induced by BA.1 infection and vaccination; BA.2.75 and BA.5 subvariants can evade the humoral immunity elicited by BA.5 breakthrough infection.

  • Prospectively alerted the emergence and prevalence of convergent mutants such as XBB.

  • Predicting the evolution of XBB sublineages: XBB* subvariants carrying 486P mutation (such as XBB.1.5 and XBB.1.9.2) would acquire additional immune-escape mutations due to enhanced hACE2-binding affinity.



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