Fig. 1: Characterizations of additional mutations in the context of BA.4/5 to enhance virus evasion from antibodies of breakthrough infections. | Cell Discovery

Fig. 1: Characterizations of additional mutations in the context of BA.4/5 to enhance virus evasion from antibodies of breakthrough infections.

From: Evolving spike mutations in SARS-CoV-2 Omicron variants facilitate evasion from breakthrough infection-acquired antibodies

Fig. 1: Characterizations of additional mutations in the context of BA.4/5 to enhance virus evasion from antibodies of breakthrough infections.The alternative text for this image may have been generated using AI.

a Frequencies of RBD mutations in different waves; 34 representative RBD mutations were selected for functional assessment. Schematics of involved mutations were presented in the BA.4/5 spike. L517 is not marked in the structure diagram as it is not on the RBD surface. NTD N-terminal domain, RBD receptor binding site, FP fusion peptide, HR heptad repeat, TM transmembrane. b Cross-neutralization profiles of the 3d-BA.4/5-HCPs (n = 18) and 3d-BA.2-HCPs (n = 17) to BA.4/5-RBD mutants (left panel) and newly emerged variants (right panel). Dark shadows indicate the limits of detections (ID50 = 20). The broken lines indicate the nAb GMT of HCPs against BA.4/5 for comparisons. c Proportions of HCPs according to the strata of nAb decrease against RBD mutants relative to BA.4/5. d, e Correlation of the nAb GMT of the breakthrough infection-derived HCPs against various BA.4/5-RBD mutants, with the R2 of exponential growth fit of the prevalence of the corresponding mutations in BA.4/5 (d) and BA.2 (e) strains. f Correlation of the nAb GMT titers in 3d-BA.4/5-HCPs and 3d-BA.2-HCPs against various BA.4/5-RBD mutants. In neutralization, assays of N417T, V445A, V445P, and G446S mutants, two samples in the 3d-BA.2-HCPs group, were not detected due to limited sample volume. g Neutralization profiles of the 3d-BA.4/5-HCPs against pseudoviruses bearing BA.4/5-XBB chimeric spikes. The antibody data against XBB, BA.4/5, and BA.4/5 bearing F490S, N460K, D339H, R346T, and V445P were the same as panel b. For panels g and f, data were plotted as the geometric mean with a 95% confidence interval. Mutations with sequence numbers < 10 from May to October 2022 were not fitted. In the correlation analysis of R2 with nAb titers, R2 for mutations with a decreasing trend (k < 0) in the time frame was assigned as 0. P values in panel b were calculated using two-tailed Wilcoxon signed-rank tests of paired samples; P values in panel d–f were the result of a two-tailed test for the Spearman rank correlation coefficient. *P < 0.05. **P < 0.01. ***P < 0.001. ****P < 0.0001. ns not significant, nAb neutralizing antibody, ID50 half-maximal inhibitory dilution.

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