Abstract
As Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to spread, characterization of its antibody epitopes, emerging strains, related coronaviruses, and even the human proteome in naturally infected patients can guide the development of effective vaccines and therapies. Since traditional epitope identification tools are dependent upon pre-defined peptide sequences, they are not readily adaptable to diverse viral proteomes. The Serum Epitope Repertoire Analysis (SERA) platform leverages a high diversity random bacterial display library to identify proteome-independent epitope binding specificities which are then analyzed in the context of organisms of interest. When evaluating immune response in the context of SARS-CoV-2, we identify dominant epitope regions and motifs which demonstrate potential to classify mild from severe disease and relate to neutralization activity. We highlight SARS-CoV-2 epitopes that are cross-reactive with other coronaviruses and demonstrate decreased epitope signal for mutant SARS-CoV-2 strains. Collectively, the evolution of SARS-CoV-2 mutants towards reduced antibody response highlight the importance of data-driven development of the vaccines and therapies to treat COVID-19.
Highlights
As Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to spread, characterization of its antibody epitopes, emerging strains, related coronaviruses, and even the human proteome in naturally infected patients can guide the development of effective vaccines and therapies
We present in this paper the application of Serum Epitope Repertoire Analysis (SERA), a high throughput, random bacterial peptide display technology that enables assessment of SARS-CoV-2 seropositivity and high-resolution mapping of epitopes across any arbitrary proteome, including wild-type SARS-CoV-2, its mutant strains, common coronaviruses, and the human proteome
While conventional serology is a cornerstone of infectious disease diagnosis, the COVID-19 pandemic has raised many questions not answered by these testing modalities alone
Summary
As Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to spread, characterization of its antibody epitopes, emerging strains, related coronaviruses, and even the human proteome in naturally infected patients can guide the development of effective vaccines and therapies. Along with the initial step of defining an effective vaccine for the immediate crisis, factors such as viral mutation rate and the uncertainty of long-term immunity could play a large role in ongoing management. It is unclear if it will be possible to develop “sterilizing immunity” to the virus, preventing infection completely[18,19,20]. We present in this paper the application of Serum Epitope Repertoire Analysis (SERA), a high throughput, random bacterial peptide display technology that enables assessment of SARS-CoV-2 seropositivity and high-resolution mapping of epitopes across any arbitrary proteome, including wild-type SARS-CoV-2, its mutant strains, common coronaviruses, and the human proteome
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