Highly versatile antibody binding assay for the detection of SARS-CoV-2 infection and vaccination

Pratik Datta, Rahul Ukey, Natalie Bruiners, William Honnen, Mary O. Carayannopoulos, Charles Reichman, Alok Choudhary, Alberta Onyuka, Deborah Handler, Valentina Guerrini, Pankaj K. Mishra, Hannah K. Dewald, Alfred Lardizabal, Leeba Lederer, Aliza L. Leiser, Sabiha Hussain, Sugeet K. Jagpal, Jared Radbel, Tanaya Bhowmick, Daniel B. Horton, Emily S. Barrett, Yingda L. Xie, Patricia Fitzgerald-Bocarsly, Stanley H. Weiss, Melissa Woortman, Heta Parmar, Jason Roy, Maria Gloria Dominguez-Bello, Martin J. Blaser, Jeffrey Carson, Reynold A. Panettieri, Steven Libutti, Henry F. Raymond, Abraham Pinter, Maria Laura Gennaro

Publication Date: 12/01/2021

Monitoring the burden and spread of infection with the new coronavirus SARS-CoV-2, whether within small communities or in large geographical settings, is of paramount importance for public health purposes. Serology, which detects the host antibody response to the infection, is the most appropriate tool for this task, since virus-derived markers are most reliably detected during the acute phase of infection. Here we show that our ELISA protocol, which is based on antibody binding to the Receptor Binding Domain (RBD) of the S1 subunit of the viral Spike protein expressed as a novel fusion protein, detects antibody responses to SARS-CoV-2 infection and vaccination. We also show that our ELISA is accurate and versatile. It compares favorably with commercial assays widely used in clinical practice to determine exposure to SARS-CoV-2. Moreover, our protocol accommodates use of various blood- and non-blood-derived biospecimens, such as breast milk, as well as dried blood obtained with microsampling cartridges that are appropriate for remote collection. As a result, our RBD-based ELISA protocols are well suited for seroepidemiology and other large-scale studies requiring parsimonious sample collection outside of healthcare settings.