Reevaluation of antibody-dependent enhancement of infection in anti-SARS-CoV-2 therapeutic antibodies and mRNA-vaccine antisera using FcR- and ACE2-positive cells

Figure 1. Anti-SARS-CoV-2 neutralizing mAbs, casirivimab and imdevimab, have the potential to cause ADE of infection. (A,B) Clone 35 cells (2 × 104/well in a 96-well flat plate) were cultured with SARS-CoV-2 (original strain, 4 × 103 copies/μL) in the presence (N = 3) or absence (N = 3–6, control culture) of serially-diluted Cas, Imd, or isotype control Abs as indicated. Three days later, the amount of virus in culture SNs was measured by qPCR. The increase of virus progeny in SNs is expressed as the fold increase compared with the amount of viruses cultured in the absence of Abs. (C) Clone 35 cells were cultured with SARS-CoV-2 in the presence or absence of a constant dose of the indicated Abs (final 1 ng/mL each) as in (A). Each symbol represents individual experiments. (D,E) Clone 35 cells were cultured as in (A), but with a low dose of SARS-CoV-2 (40 copies/μL). Each symbol represents individual wells (N = 20 per group).

Figure 2. Sotrovimab mAb has no potential to cause ADE of infection. Clone 35 cells (2 × 104/well in a 96-well flat plate) were cultured with SARS-CoV-2 (original or Omicron strain) in the presence (N = 3) or absence (N = 3–6, control culture) of serially-diluted Cas (A,C) or Sot (B,D) mAb. Three days later, the amount of virus in culture SNs was measured by qPCR. The increase of virus progeny in SNs is expressed as the fold increase compared with the amount of viruses cultured in the absence of mAb on a linear scale (A,B) or log scale (C,D).

Figure 3. ADE potential in sera collected from mRNA-vaccinated volunteers. (A) Clone 35 cells (2 × 104/well in a 96-well flat plate) were cultured with SARS-CoV-2 (original strain, 4 × 103 copies/μL) in the presence (N = 3) or absence (N = 3–6, control culture) of serially-diluted sera from the same individual (HC2). Sera were collected at different time points after the first vaccination (on day 27) and second vaccination (on days 20, 52, and 98) as indicated in the insert. (B–D) Sera were collected on day 98 (B), day 133 (C), and day 175 (D) after the second vaccination from six healthy control volunteers (HC1-6, see insert in (B)) and added to the cultures as in (A). Three days later, the amount of virus in culture SNs was measured by qPCR. The increase of virus progeny in SNs is expressed as the fold increase compared with the amount of viruses cultured in the absence of serum on a linear scale (this figure) or log scale (Supplemental Fig. 6).