Proteome-Wide\nAnalysis of Antibody Responses in Asymptomatic Omicron BA.2-Infected\nIndividuals at the Amino Acid Resolution

Humoral immunity plays a critical\nrole in clearing SARS-CoV-2\nduring viral invasion. However, the proteome-wide characteristics\nof antibody responses in individuals infected with Omicron variant,\nboth asymptomatic and symptomatic, remain poorly understood. We profiled\nthe serum antibodies from 108 individuals, including healthy controls\nand those infected with Omicron BA.2, using a SARS-CoV-2 proteome\nmicroarray at the amino acid resolution. We constructed a landscape\nof B-cell epitopes across the SARS-CoV-2 proteome in symptomatic and\nasymptomatic individuals. Immunodominant epitopes were mainly derived\nfrom S, N, Nsp3, M, and ORF3a proteins, with some epitopes overlapping\nwith T-cell epitopes. Using machine learning, we identified a proteomic\nsignature capable of distinguishing asymptomatic individuals from\nhealthy controls in both training and validation cohorts, achieving\nAUCs of 0.988 and 0.857, respectively. These findings provide crucial\nimmunological insights into BA.2 infections of the Omicron and have\nimplications for future COVID-19 diagnostics and therapeutics.