Uncovering a conserved vulnerability site in SARS-CoV-2 by a human antibody (2021)
Figure 2

Fig 2. FD20 is resistant to several escape SARS-CoV-2 S mutants.

(A) Neutralization assay of FD20 using SARS-CoV-2 pp harboring spike derived from four Variants of Concern as indicated. Mean ± s.d. are plotted (n = 3 biological replicates). Numbers in brackets indicate IC50 values in nM.

(B) Microneutralization assay of FD20 against authentic SARS-CoV-2 Wuhan isolate (hCoV-19/China/CAS-B001/2020). The protective effect of antibody was assessed using cells infected with a high viral dose (2,000 TCID50 mL-1). Data are from a single experiment performed in octuplicates. Numbers in brackets indicate IC50 values in nM.

(C) The plaque-reduction neutralization assay using two authentic SARS-CoV-2 strains: the Germany isolate (BetaCoV/Munich/BavPat1/2020) and UK/B1.1.7. Mean ± s.d. are plotted (n = 3 biological replicates). Numbers in brackets indicate IC50 values in nM.

(D) IC50 (up, in nM) and normalized IC50 folds (bottom, normalized against the wild-type) of FD20 and control antibodies measured using different SARS-CoV-2 pp harboring S mutants or variants. E406W is an escape mutant from REG10933 and REG10987 cocktail generated in vitro (Starr et al, 2021). K417N is an escape mutant for CB6 (LyCoV.016) and is present in the B.1.351 lineage first identified in South Africa (Li et al, 2020; Starr et al, 2021). Y453F increases the ACE2 binding affinity, and with A475V and F490L, is found in independent mink-related SARS-CoV-2 variants (Larsen et al, 2021; Oude Munnink et al, 2021) identified in Denmark and the Netherlands (B1.1 and B.1.1.298) that may escape human antisera and REG10933 (Starr et al, 2021). D614G appeared early during the pandemic and is now the dominant form worldwide, and is associated with other mutations in new variants of concern (Korber et al, 2020). A222V and S477N are described in 20A.EU1 (B.1.177) and 20A.EU2 (B.1.160) that emerged in early summer 2020 and subsequently spread to multiple locations in Europe at the end of 2020 (Lemey et al, 2021). N439K is in B.1.141, B.1.258, and in mink strains; it increases affinity to ACE2 and reduces neutralization of sera from convalescent patients (Thomson et al, 2021). Finally, ∆69/70-N501Y-D614G are characteristic mutations in RBD for the UK/B.1.1.7 lineage (501Y.V1) (Leung et al, 2021), one of the three fast-spreading new variants of SARS-CoV-2 that have emerged in recent months. The B1.351 (501Y.V2) identified in South Africa has raised concerns that the efficacy of current vaccines and therapeutic monoclonal antibodies could be threatened (Tegally et al, 2021). The P.1 (Gamma or Brazilian variant) has contributed to a surge in cases in the northern city of Manaus and it has been reported in January 2021 in Japan. The highly contagious B.1.617.2, commonly known as the Delta, is currently responsible for over 90% of the cases in the UK and over 80% of the cases in the USA and has caused concerns about vaccine efficacy (Lopez Bernal et al, 2021). The background is color-colored based on the neutralizing activity (up) or change in neutralizing activity (bottom). IC50 values are the mean from at least two independent experiments.

Source data for A-D, including exact n for D, are available online.