No substantial pre-existing B cell immunity against SARS-CoV-2 in healthy adults

Ercanoglu, Meryem Seda; Gieselmann, Lutz; Dähling, Sabrina; Poopalasingam, Nareshkumar; Detmer, Susanne; Koch, Manuel; Korenkov, Michael; Halwe, Sandro; Klüver, Michael; Di Cristanziano, Veronica; Janicki, Hanna; Schlotz, Maike; Worczinski, Johanna; Gathof, Birgit; Gruell, Henning; Zehner, Matthias; Becker, Stephan; Vanshylla, Kanika; Kreer, Christoph; Klein, Florian

Pre-existing immunity against SARS-CoV-2 may have critical implications for our understanding of COVID-19 susceptibility and severity. Various studies recently provided evidence of pre-existing T cell immunity against SARS-CoV-2 in unexposed individuals. In contrast, the presence and clinical relevance of a pre-existing B cell immunity remains to be fully elucidated. Here, we provide a detailed analysis of the B cell response to SARS-CoV-2 in unexposed individuals. To this end, we extensively investigated the memory B cell response to SARS-CoV-2 in 150 adults sampled pre-pandemically. Comprehensive screening of donor plasma and purified IgG samples for binding and neutralization in various functional assays revealed no substantial activity against SARS-CoV-2 but broad reactivity to endemic betacoronaviruses. Moreover, we analyzed antibody sequences of 8,174 putatively SARS-CoV-2-reactive B cells on a single cell level and generated and tested 158 monoclonal antibodies. None of the isolated antibodies displayed relevant binding or neutralizing activity against SARS-CoV-2. Taken together, our results show no evidence of relevant pre-existing antibody and B cell immunity against SARS-CoV-2 in unexposed adults.