High-resolution epitope mapping and characterization of SARS-CoV-2 antibodies in large cohorts of subjects with COVID-19
Winston Haynes, Kathy Kamath, Joel Bozekowski, Elisabeth Baum, Melissa Campbell, Arnau Casanovas‐Massana, Patrick S. Daugherty, Charles S. Dela Cruz, Abhilash Dhal, Shelli Farhadian, Lynn Fitzgibbons, John Fournier, Michael Jhatro, Gregory J. Jordan, Jon Klein, Carolina Lucas, Debra Kessler, Larry L. Luchsinger, Brian Martinez, M. Catherine Muenker, Lauren Pischel, Jack Reifert, Jaymie R. Sawyer, Rebecca Waitz, Elsio A. Wunder, Minlu Zhang, Yale IMPACT Team, Kelly Anastasio, Michael H. Askenase, Natasha C. Balkcom, Maria Batsu, Santos Bermejo, Kristina Brower, Molly L. Bucklin, Staci Cahill, Yiyun Cao, Michael Chiorazzi, Caitlin J. Chun, Rupak Datta, Giuseppe DeIuliis, Coriann E. Dorgay, Rebecca Earnest, John Fournier, Bertie Geng, Ryan Handoko, William Khoury-Hanold, Roy S. Herbst, Lynda Knaggs, Maxine Kuang, Sarah Lapidus, Zitong Lin, Peiwen Lu, Tianyang Mao, Anjelica Martin, Irene Matos, David McDonald, Maksym Minasyan, Adam J. Moore, Nida Naushad, Allison Nelson, Jessica Nouws, Ángela Núñez, Hong‐Jai Park, Xiaohua Peng, Alexander J. Robertson, Tyler Rice, Kadi-Ann Rose, Wade L. Schulz, Lorenzo R. Sewanan, Lokesh Kumar Sharma, Denise Shepard, Julio Silva, Michael Simonov, Mikhail Smolgovsky, Nicole Sonnert, Ariktha Srivathsan, Yvette Strong, Codruta Todeasa, Jordan Valdez, Sofia Velazquez, Pavithra Vijayakumar, Elizabeth B. White, Alice Zhao, Akiko Iwasaki, Albert I. Ko, John Shon
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.