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. 2021 Dec;57(6):502-509.
doi: 10.1007/s11262-021-01871-8. Epub 2021 Oct 4.

Sensitivity of two SARS-CoV-2 variants with spike protein mutations to neutralising antibodies

Affiliations

Sensitivity of two SARS-CoV-2 variants with spike protein mutations to neutralising antibodies

Katharina Müller et al. Virus Genes. 2021 Dec.

Abstract

SARS-CoV-2 infections elicit a humoral immune response capable of neutralising the virus. However, multiple variants have emerged with mutations in the spike protein amongst others, the key target of neutralising antibodies. We evaluated the neutralising efficacy of 89 serum samples from patients, infected with SARS-CoV-2 in the beginning of 2020, against two virus variants isolated from acutely infected patients and harbouring spike protein mutations. One isolate was assigned to lineage B.1.351 (MUC-IMB-B.1.351) whilst the other (MUC-484) was isolated from an immunocompromised patient, sharing some but not all mutations with B.1.351 and representing a transitional variant. Both variants showed a significant reduction in neutralisation sensitivity compared to wild-type SARS-CoV-2 with MUC-IMB-B.1.351 being almost completely resistant to neutralisation. The observed reduction in neutralising activity of wild-type-specific antibodies against both variants suggests that individual mutations in the spike protein are sufficient to confer a potent escape from the humoral immune response. In addition, the effect of escape mutations seems to accumulate, so that more heavily mutated variants show a greater loss of sensitivity to neutralisation up to complete insensitivity as observed for MUC-IMB-B.1.351. From a clinical point of view, this might affect the efficacy of (monoclonal) antibody treatment of patients with prolonged infections as well as patients infected with variants other than the donor. At the same, this could also negatively influence the efficacy of current vaccines (as they are based on wild-type spike protein) emphasising the need to thoroughly surveil the emergence and distribution of variants and adapt vaccines and therapeutics accordingly.

Keywords: B.1.351; COVID-19; Immune escape; Mutation E484K; Neutralising antibodies; SARS-CoV-2; Variants of concern.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Lollipop plots of all three SARS-CoV-2 strains examined in this study showing all nonsynonymous mutations in their respective genomes. A MUC-IMB-B.1.351 holds 26 mutations distributed over the genome. B MUC-484 shares only a few mutations with lineage B.1.351. C MUC-IMB-1 was used as WT SARS-CoV-2 reference strain
Fig. 2
Fig. 2
Comparison of MUC-IMB-1 and MUC-IMB-B.1.351 demonstrates a significant decrease in sensitivity towards NAbs (A) Side by-side comparison of NAbs titres against WT (orange) and MUC-IMB-B.1.351 (purple). The greatest decrease was observed in a sample, which dropped from an initial titre of 177 to no neutralising effect against B.1.351 (red). (B) All but nine samples (blue) show a complete loss of neutralising activity (black). All samples that tested negative for NAbs against WT remained negative when tested against MUC-IMB-B.1.351 (grey). (∑ samples: 89, the number of overlapping samples is shown in the respective circle)
Fig. 3
Fig. 3
Correlation plot reveals limited correlation between NAbs titres against MUC-IMB-1 and MUC-IMB-B.1.351 No prediction can be made about the neutralising efficacy of a serum against MUC-B.1.351 based on the NAbs titre of the same sample against WT SARS-CoV-2 and vice versa (r = 0.53, 95% CI: 0.37–0.67 Pearson regression analysis)
Fig. 4
Fig. 4
Comparison of MUC-IMB-1 and MUC-484 demonstrates an overall decrease in sensitivity towards NAbs (A) Side-by-side comparison of WT (orange) and MUC-484 (blue) reveals an overall decrease in NAbs titre levels with the exception of only two samples depicted in green, showing a lowgrade increase in titre level from 11 to 27.6 and 7.8 to 12.5, respectively. (B) Whilst one third of samples was still able to neutralise MUC-484 (blue), a notable decrease in titre levels can be observed for all but two of those samples with a median decrease of 97.1%. Two samples show an increase in neutralising activity (green). The remaining two-thirds of the samples show a complete loss of neutralising efficacy against MUC-IMB-1 (black) whilst all 16 samples that tested negative for NAbs against MUC-IMB-1 remained negative when tested against MUC-484 (grey). (∑ samples: 80; the number of overlapping samples is shown in the respective circle)
Fig. 5
Fig. 5
Correlation plot reveals very limited correlation between NAbs titres against MUC-IMB-1 and MUC-484 Based on the very limited correlation, no predictions can be made about the neutralising effect of a serum against MUC-484 based on the titre of the same sample against WT SARS-CoV-2 (r = 0.37, 95% CI: 0.17–0.55 Pearson regression analysis)

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Supplementary concepts