SARS-CoV-2 antibody signatures robustly predict diverse antiviral functions relevant for convalescent plasma therapy

Abstract

Convalescent plasma has emerged as a promising COVID-19 treatment. However, the humoral factors that contribute to efficacy are poorly understood. This study functionally and phenotypically profiled plasma from eligible convalescent donors. In addition to viral neutralization, convalescent plasma contained antibodies capable of mediating such Fc-dependent functions as complement activation, phagocytosis and antibody-dependent cellular cytotoxicity against SARS-CoV-2. These activities expand the antiviral functions associated with convalescent plasma and together with neutralization efficacy, could be accurately and robustly from antibody phenotypes. These results suggest that high-throughput profiling could be used to screen donors and plasma may provide benefits beyond neutralization.

Antibody responses to endemic coronaviruses modulate COVID-19 convalescent plasma functionality

“…(8) We also measured ADCP, ADCC, and ADCD for each plasma donation. (13) We recently used a massively multiplexed For all plasma samples, we measured antibody binding to each 56 amino acid peptide in the library. In each group of samples, we examined two virus-level reactivity scores: (i) aggregate reactivity across all peptides from each virus ( Figure 1B), and (ii) aggregate reactivity across the frequently reactive (dominant) peptides from each virus ( Figure 1C).…”

“…The antibody response to CoV2 is highly variable in terms of titer, (8,9) avidity, (10) antigenic preference, (11,12) kinetics of induction, (9) isotype usage, (13) and functionally protective capacity. (13) Differential pre-existing immune responses to endemic HCoVs may contribute to the large variation in CoV2 antibody response. Recent studies of pre-pandemic plasma identified a low prevalence of pre-existing reactivity against the S2 subunit of the CoV2 spike (S) protein.…”

“…Recent studies of pre-pandemic plasma identified a low prevalence of pre-existing reactivity against the S2 subunit of the CoV2 spike (S) protein. (13,14) S2 contains structures that are critical for virus entry into cells, such as the fusion peptide (FP), which is conserved across coronaviruses; sequence conservation in this region may explain the presence of these CoV2-reactive antibodies prior to the COVID -19 pandemic. (12) Boosting of pre-existing HCoV antibodies in response to infection with CoV2 may occur in the absence of antibody functionality, a phenomenon referred to as "original antigenic sin."…”

“…Cytopathic effect was scored following 4% formaldehyde fixation and staining with Napthol Blue-Black, and an AUC, representing plasma neutralizing activity, was determined.Phagocytosis assay ADCP was assessed as described (13). Briefly, uptake of fluorescent RBD-conjugated microspheres by monocytic human THP-1 cells in the presence of CCP was defined by flow cytometry.CD16 reporter assayFcgRIIIa ligation activity was defined as previously reported(13)as a surrogate of ADCC activity.…”

Longitudinal analysis of humoral immunity against SARS-CoV-2 Spike in convalescent individuals up to 8 months post-symptom onset

“…Fc-mediated effector activity of antibodies has been recently shown to correlate with reduced disease severity and mortality (21). Antibodies capable of mediating Fc-dependant functions, such as antibody-dependent phagocytosis and ADCC, have been isolated from convalescent donors (35). Importantly, Fc-mediated effector activity was shown to protect from SARS-CoV-2 10 infection in adapted mice and hamster models (9,19,32).…”