Competitive SARS-CoV-2 Serology Reveals Most Antibodies Targeting the Spike Receptor-Binding Domain Compete for ACE2 Binding

MSphere
James R ByrnesJames A Wells

Abstract

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread around the world, there is an urgent need for new assay formats to characterize the humoral response to infection. Here, we present an efficient, competitive serological assay that can simultaneously determine an individual's seroreactivity against the SARS-CoV-2 Spike protein and determine the proportion of anti-Spike antibodies that block interaction with the human angiotensin-converting enzyme 2 (ACE2) required for viral entry. In this approach based on the use of enzyme-linked immunosorbent assays (ELISA), we present natively folded viral Spike protein receptor-binding domain (RBD)-containing antigens via avidin-biotin interactions. Sera are then competed with soluble ACE2-Fc, or with a higher-affinity variant thereof, to determine the proportion of ACE2 blocking anti-RBD antibodies. Assessment of sera from 144 SARS-CoV-2 patients ultimately revealed that a remarkably consistent and high proportion of antibodies in the anti-RBD pool targeted the epitope responsible for ACE2 engagement (83% ± 11%; 50% to 107% signal inhibition in our largest cohort), further underscoring the importance of tailoring vaccines to promote the development of such ...Continue Reading

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Citations

Oct 22, 2020·Nature Chemical Biology·Colton J BrackenJames A Wells
Dec 15, 2020·Advanced Drug Delivery Reviews·Carlos Cruz-TeranSamuel K Lai
Jan 19, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Murat Oz, Dietrich Ernst Lorke
Mar 27, 2021·Nature Biotechnology·Susanna K ElledgeJames A Wells
May 1, 2021·Viruses·Giulia Matusali Inmi Covid-Laboratory Team
May 14, 2021·Clinical Microbiology Reviews·Seyed Hamid Safiabadi TaliSana Jahanshahi-Anbuhi
Jun 30, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Deli HuangDavid Nemazee

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Methods Mentioned

BETA
PCR
enzyme-linked immunosorbent assays
ELISA
reverse transcription-PCR
glycosylation

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