Epitope profiling reveals binding signatures of SARS-CoV-2 immune response in natural infection and cross-reactivity with endemic human CoVs

Abstract

Highlights d Pan-coronavirus phage display library maps epitopes in patients with COVID-19 d Most immune responses target SARS-CoV-2 S, N, and ORF1ab sequences d Certain epitopes include sites of mutation in SARS-CoV-2 variants of concern d Evidence for cross-reactivity between SARS-CoV-2 and endemic human CoVs

SARS-CoV-2 Antibody Binding and Neutralization in Dried Blood Spot Eluates and Paired Plasma

“…In this study, we addressed gaps in the SARS-CoV-2 DBS field by collecting paired plasma and DBS cards from COVID-19 convalescent and SARS-CoV-2-vaccinated individuals. We assessed the agreement between sample types for several antibody-based methods, including a widely used receptor-binding domain (RBD) enzyme-linked immunosorbent assay (ELISA) ( 37 , 38 ), a comprehensive phage display approach ( 39 ), and a SARS-CoV-2 spike neutralization assay ( 40 ), which we optimized here for higher throughput. For all approaches, we found consistently high agreement between sample types, including between paired plasma and eluates from self-collected fingerstick DBS cards.…”

Possible Targets of Pan-Coronavirus Antiviral Strategies for Emerging or Re-Emerging Coronaviruses

“…By using high-throughput genome-scale screenings, such as phage display library, CRISPR-based library, and electro-chemiluminescence-based multiplex assay [ 57 , 90 , 103 , 104 ], it is hopeful that we will identify conserved cross-reactive epitopes or domains in coronaviruses and host proteins, which can be used for pan-coronavirus antiviral strategies, and design small-molecule drugs and peptides or identify existing pharmaceuticals and herbal medicines specifically targeting coronaviruses infection, such as viral spike protein-receptor binding and fusion, viral polymerase, nonstructural protein, and proteases. Moreover, other antiviral strategies are also required for pan-coronavirus inhibition.…”

“…As reported, naïve antibodies expressed by the naïve B cell can neutralize SARS-CoV, SARS-like WIV1-CoV, SARS-CoV-2 and its mutants via recognition of the viral receptor-binding domain [ 89 ]. Cross-reactive epitopes are mainly located in the viral S, N, and ORF1ab, among which the S2 subunit of the spike protein contains the most promising cross-reactive epitopes, but the immune response induced by ORF1ab epitopes shows high individual specificity [ 90 ]. Six monoclonal antibodies that cross-reacted with the S proteins of SARS-CoV, SARS-CoV-2, and other coronaviruses via diverse epitopes were identified [ 91 ].…”

Potential autoimmunity resulting from molecular mimicry between SARS-CoV-2 Spike and human proteins

“…It is also interesting to note that antibodies against a TQLPP-containing peptide were found in the serum of pre-pandemic, unexposed individuals (Stoddard et al 2021). Prior infection with a different human coronavirus cannot explain the cross-reactivity observed in the unexposed group because TQLPP is situated in a region with low amino acid conservation (Stoddard et al 2021). Rather, this suggests the presence of an antibody for an unknown epitope with affinity for the TQLPP region in the Spike protein.…”