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

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

doi:10.1016/j.isci.2022.103951

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

iScience. 2022 Mar 18;25(3):103951. doi: 10.1016/j.isci.2022.103951. Epub 2022 Feb 19.

Authors

Meryem Seda Ercanoglu¹, Lutz Gieselmann^{1

2}, Sabrina Dähling¹, Nareshkumar Poopalasingam¹, Susanne Detmer¹, Manuel Koch^{3

4}, Michael Korenkov¹, Sandro Halwe^{5

6}, Michael Klüver^{5

6}, Veronica Di Cristanziano¹, Hanna Janicki¹, Maike Schlotz¹, Johanna Worczinski¹, Birgit Gathof⁷, Henning Gruell^{1

2}, Matthias Zehner^{1

2}, Stephan Becker^{5

6}, Kanika Vanshylla¹, Christoph Kreer¹, Florian Klein^{1

2

3}

Affiliations

¹ Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
² German Center for Infection Research, Partner Site Bonn-Cologne, 50931 Cologne, Germany.
³ Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany.
⁴ Institute for Dental Research and Oral Musculoskeletal Biology and Center for Biochemistry, University of Cologne, 50931 Cologne, Germany.
⁵ Institute of Virology, Philipps University Marburg, Hans-Meerwein-Straße 2, 35042 Marburg, Germany.
⁶ German Center for Infection Research, Partner Site Giessen-Marburg-Langen, 35043 Marburg, Germany.
⁷ Institute of Transfusion Medicine, Faculty of Medicine and University Hospital Cologne, 50937 Cologne, Germany.

Abstract

Preexisting immunity against SARS-CoV-2 may have critical implications for our understanding of COVID-19 susceptibility and severity. The presence and clinical relevance of a preexisting B cell immunity remain to be fully elucidated. Here, we provide a detailed analysis of the B cell immunity to SARS-CoV-2 in unexposed individuals. To this end, we extensively investigated SARS-CoV-2 humoral immunity 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 at a single cell level and generated and tested 158 monoclonal antibodies. None of these antibodies displayed relevant binding or neutralizing activity against SARS-CoV-2. Taken together, our results show no evidence of competent preexisting antibody and B cell immunity against SARS-CoV-2 in unexposed adults.

Keywords: Immune response; Immunity; Virology.