Open AccessAntibody Affinity Governs the Inhibition of SARS-CoV-2 Spike/ACE2 Binding in Patient Serum
Author(s) -
Sebastian Fiedler,
Monika A. Piziorska,
Viola Denninger,
Alexey S. Morgunov,
Alison Ilsley,
Anisa Y Malik,
Matthias M. Schneider,
Sean R. A. Devenish,
Georg Meisl,
Vasilis Kosmoliaptsis,
Adriano Aguzzi,
Heike Fiegler,
Tuomas P. J. Knowles
Publication year - 2021
Publication title -
acs infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.324
H-Index - 39
ISSN - 2373-8227
DOI - 10.1021/acsinfecdis.1c00047
Subject(s) - antibody , neutralization , receptor , viral entry , virology , biology , virus , antigen , chemistry , immunology , viral replication , biochemistry
The humoral immune response plays a key role in suppressing the pathogenesis of SARS-CoV-2. The molecular determinants underlying the neutralization of the virus remain, however, incompletely understood. Here, we show that the ability of antibodies to disrupt the binding of the viral spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor on the cell, the key molecular event initiating SARS-CoV-2 entry into host cells, is controlled by the affinity of these antibodies to the viral antigen. By using microfluidic antibody-affinity profiling, we were able to quantify the serum-antibody mediated inhibition of ACE2-spike binding in two SARS-CoV-2 seropositive individuals. Measurements to determine the affinity, concentration, and neutralization potential of antibodies were performed directly in human serum. Using this approach, we demonstrate that the level of inhibition in both samples can be quantitatively described using the dissociation constants ( K D ) of the binary interactions between the ACE2 receptor and the spike protein as well as the spike protein and the neutralizing antibody. These experiments represent a new type of in-solution receptor binding competition assay, which has further potential applications, ranging from decisions on donor selection for convalescent plasma therapy, to identification of lead candidates in therapeutic antibody development, and vaccine development.