Rational design and standardization of serology diagnostics using immunoaffinity-targeted proteomics assays

Current design of serology antibody tests is driven by convenience, speed of manufacturing, and affordability. Limitations of common serology tests include cross-reactivity and lack of standardization, which decrease diagnostic specificity and make such tests inappropriate to screen the general asymptomatic populations with low prevalence of COVID-19. Viral antigens used in the common tests assume detection of binding antibodies, but not necessarily neutralizing antibodies, further limiting the value of such tests. In our study, we will focus on rational design and standardization of serology diagnostics of SARS-CoV-2. We will utilize immunoassays and quantitative immunoaffinity-targeted proteomics assays to discover, verify and validate combinations of antigens and antibody isotypes which provide the highest diagnostic specificity and sensitivity. Unlike semi-quantitative serology immunoassays, our proteomic assays are quantitative, have no cross-reactivity, and provide "gold standard" solutions for inter-laboratory and international standardization of serology tests. Our study will facilitate improvements of diagnostic specificity of existing serology immunoassays, thus enabling population screening for the acquired immunity.