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. 2021 Dec;18(12):2673-2675.
doi: 10.1038/s41423-021-00779-5. Epub 2021 Oct 25.

The spike protein of SARS-CoV-2 variant A.30 is heavily mutated and evades vaccine-induced antibodies with high efficiency

Affiliations

The spike protein of SARS-CoV-2 variant A.30 is heavily mutated and evades vaccine-induced antibodies with high efficiency

Prerna Arora et al. Cell Mol Immunol. 2021 Dec.
No abstract available

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
SARS-CoV-2 A.30 enters certain cell lines with increased efficiency and evades antibody-mediated neutralization. a Schematic overview and domain organization of the SARS-CoV-2 S proteins studied. Abbreviations: RBD, receptor-binding domain; TD, transmembrane domain. b Pseudotyped particles bearing the indicated S proteins were inoculated onto different cell lines, and transduction efficiency was quantified by measuring virus-encoded luciferase activity in cell lysates at 16–18 h postinoculation. Presented are the average (mean) data from six to 12 biological replicates (each conducted with technical quadruplicates) for which transduction was normalized against SARS-CoV-2 S B.1 (= 1). Error bars indicate the standard error of the mean (SEM). The statistical significance of differences between B.1 and A.30, B.1.525, or B.1.351 was analyzed by two-tailed Student’s t-test with Welch correction (p > 0.05, not significant [ns]; p ≤ 0.05, *; p ≤ 0.01, **; p ≤ 0.001, ***). See also Supplemental information, Fig. S1b. c Neutralization of SARS-CoV-2 B.1, A.30, B.1.525, and B.1.351 by monoclonal antibodies used for COVID-19 therapy or an unrelated control antibody (Supplemental information, Fig. S1d). Pseudotyped particles were incubated for 30 min at 37 °C in the presence of increasing concentrations (0.00002, 0.0002, 0.002, 0.02, 0.2, 2 µg/ml) of the indicated monoclonal antibodies or an unrelated control antibody before being inoculated onto Vero cells. Infection efficiency was quantified by measuring virus-encoded luciferase activity in cell lysates at 16–18 h postinoculation. Presented are average (mean) data from a single biological replicate (conducted with technical quadruplicates) for which infection was normalized against samples that did not contain antibody (= 0% inhibition). The data were confirmed in a separate independent experiment. Error bars indicate the standard deviation. d Neutralization of SARS-CoV-2 B.1, A.30, B.1.525, and B.1.351 by antibodies in convalescent plasma. Pseudotyped particles bearing the indicated S proteins were incubated for 30 min in the presence of different dilutions of convalescent plasma (n = 9). Infection efficiency was determined as described for Fig. 1b and used to calculate the plasma dilution factor leading to a 50% reduction in S protein-driven cell entry (neutralizing titer 50, NT50). Data from a total of nine convalescent plasma samples are presented (black lines and numerical values indicate the median NT50). In addition, for each plasma, the fold reduction in NT50 between SARS-CoV-2 B.1 (set as 1) and the indicated variants was calculated (gray bars indicate the median). The statistical significance of differences between the indicated groups was analyzed by a two-tailed Mann–Whitney test with a 95% confidence level (p > 0.05, ns; p ≤ 0.05, *; p ≤ 0.01, **; p ≤ 0.001, ***). e The experiment was performed as described in Panel d, but serum from ChAdOx1 nCoV-19/ChAdOx1 nCoV-19 (AZ/AZ; n = 23), BNT162b2/BNT162b2 (BNT/BNT; n = 12) or ChAdOx1 nCoV-19/BNT162b2 (AZ/BNT; n = 6)-vaccinated individuals was investigated. Numbers in the bar graphs “B.1 vs. A.30” and “B.1 vs. B.1.525” indicate the number of overlapping data points (dots)

References

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Supplementary concepts