SERUM PROTEOMICS REVEALS HIGH-AFFINITY AND CONVERGENT ANTIBODIES BY TRACKING SARS-COV-2 HYBRID IMMUNITY TO EMERGING VARIANTS OF CONCERN MANUSCRIPT

Anand Patel ^* Thiago Lima Richard Carson Qiulong Huang Stefano R Bonissone Natalie Castellana

• Abterra Biosciences, Inc., San Diego, California, United States

The rapid spread of SARS-CoV-2 and continuing impact on human health has prompted the need for effective and rapid development of monoclonal antibody therapeutics. In this study, we interrogate polyclonal antibodies in serum and B cells from whole blood of three donors with SARS-CoV-2 immunity to find high-affinity anti-SARS-CoV-2 antibodies to escape variants. Serum IgG antibodies were selected by affinity to the receptor-binding domain (RBD) and non-RBD sites on the spike protein of Omicron subvariant B.1.1.529 from each donor. Antibodies were analyzed by bottomup mass spectrometry, and matched to single-and bulk-cell sequenced repertoires for each donor. Antibodies observed in serum were recombinantly expressed, and characterized to assess domain binding, cross-reactivity between different variants, and capacity to inhibit RBD binding to host protein. Donors infected with early Omicron subvariants had serum antibodies with subnanomolar affinity to RBD that show binding activity to a newer Omicron subvariant BQ.1.1. The donors also showed a convergent immune response. Serum antibodies and other single-and bulk-cell sequences were similar to publicly reported anti-SARS-CoV-2 antibodies, and characterized serum antibodies had the same variant-binding and neutralization profiles as their reported public sequence. The serum antibodies analyzed were a subset of anti-SARS-CoV-2 antibodies in the B cell repertoire, which demonstrates significant dynamics between the B cells and circulating antibodies in peripheral blood.