Exploring beyond clinical routine SARS-CoV-2 serology using MultiCoV-Ab to evaluate endemic coronavirus cross-reactivity

Becker, Matthias; Strengert, Monika; Junker, Daniel; Kaiser, Philipp D.; Kerrinnes, Tobias; Traenkle, Bjoern; Dinter, Heiko; Häring, Julia; Ghozzi, Stéphane; Zeck, Anne; Weise, Frank; Peter, Andreas; Hörber, Sebastian; Fink, Simon; Ruoff, Felix; Dulovic, Alex; Bakchoul, Tamam; Baillot, Armin; Lohse, Stefan; Cornberg, Markus; Illig, Thomas; Gottlieb, Jens; Smola, Sigrun; Karch, André; Berger, Klaus; Rammensee, Hans-Georg; Schenke-Layland, Katja; Nelde, Annika; Märklin, Melanie; Heitmann, Jonas S.; Walz, Juliane S.; Templin, Markus; Joos, Thomas O.; Rothbauer, Ulrich; Krause, Gérard; Schneiderhan-Marra, Nicole

The humoral immune response to SARS-CoV-2 is a benchmark for immunity and detailed analysis is required to understand the manifestation and progression of COVID-19, monitor seroconversion within the general population, and support vaccine development. The majority of currently available commercial serological assays only quantify the SARS-CoV-2 antibody response against individual antigens, limiting our understanding of the immune response. To overcome this, we have developed a multiplex immunoassay (MultiCoV-Ab) including spike and nucleocapsid proteins of SARS-CoV-2 and the endemic human coronaviruses. Compared to three broadly used commercial in vitro diagnostic tests, our MultiCoV-Ab achieves a higher sensitivity and specificity when analyzing a well-characterized sample set of SARS-CoV-2 infected and uninfected individuals. We find a high response against endemic coronaviruses in our sample set, but no consistent cross-reactive IgG response patterns against SARS-CoV-2. Here we show a robust, high-content-enabled, antigen-saving multiplex assay suited to both monitoring vaccination studies and facilitating epidemiologic screenings for humoral immunity towards pandemic and endemic coronaviruses.