NOMIS Awardee Adriano Aguzzi has published a study on medRxiv: “Population-wide Evolution of SARS-CoV-2 Immunity Tracked by a Ternary Immunoassay.” Until recently, Aguzzi has been studying the molecular basis of prion diseases (rare progressive neurodegenerative disorders), combining transgenetics with molecular and immunological techniques. “Because of our experience in high-throughput antibody screening, I felt that it was my duty to contribute to the fight against this crisis,” Aguzzi said.
Serological assays can detect anti-SARS-CoV-2 (SARS2) antibodies, but their sensitivity often comes at the expense of specificity. Here we used a Ternary Automated Blood Im-munoassay (TRABI) to assess the IgG response against SARS2 in 3,815 prepandemic plasma samples and 126 virologically and/or clinically confirmed COVID-19 samples. Posterior probabilities were calculated from 3×8 measurements of logarithmically diluted samples against the ectodomain and the receptor-binding domain of the spike protein and the nucleoprotein. We then performed 429,624 assays on 17,901 blood samples from patients of the University Hospital Zurich and from healthy blood donors. We found se-ropositivity in 44 of 8,591 patients and in 26 of 5,388 blood donors from December 2019 to May 2020. Western blotting confirmed seropositivity in COVID samples but in none of the prepandemic samples. Solution-equilibrium measurements revealed immunodominant antibodies with nanomolar affinity in COVID samples, whereas prepandemic plasma showed lower affinities despite similar titers for individual SARS2 antigens. Hence, TRABI identifies seropositive individuals in large unselected cohorts, discriminates be-tween SARS2 immunity and low-affinity crossreactivity, and is therefore suitable for large-scale nationwide screening campaigns.
Read the article on medRxiv
Professor of neuropathology and director of the Institute of Neuropathology
University of Zurich