Preexisting and de novo humoral immunity to SARS-CoV-2 in humans
Kevin W. Ng, Nikhil Faulkner, Georgina H. Cornish, Annachiara Rosa, Ruth Harvey, Saira Hussain, Rachel Ulferts, Christopher Earl, Antoni G. Wrobel, D.J. Benton, Chloë Roustan, William Bolland, R. Houston Thompson, Ana Agua‐Doce, Philip Hobson, Judith Heaney, Hannah M. Rickman, Stavroula Paraskevopoulou, Catherine Houlihan, Kirsty Thomson, Emilie Sanchez, Gee Yen Shin, Moira Spyer, Dhira Joshi, Nicola O’Reilly, P.A. Walker, Svend Kjær, Andrew Riddell, Catherine Moore, Bethany R. Jebson, Meredyth Wilkinson, Lucy Marshall, Elizabeth C. Rosser, Anna Radziszewska, Hannah Peckham, Coziana Ciurtin, Lucy R. Wedderburn, Rupert Beale, Charles Swanton, Sonia Gandhi, Brigitta Stockinger, John W. McCauley, S.J. Gamblin, Laura E. McCoy, Peter Cherepanov, Eleni Nastouli, George Kassiotis
Abstract
Zoonotic introduction of novel coronaviruses may encounter preexisting immunity in humans. Using diverse assays for antibodies recognizing SARS-CoV-2 proteins, we detected preexisting humoral immunity. SARS-CoV-2 spike glycoprotein (S)-reactive antibodies were detectable using a flow cytometry-based method in SARS-CoV-2-uninfected individuals and were particularly prevalent in children and adolescents. They were predominantly of the immunoglobulin G (IgG) class and targeted the S2 subunit. By contrast, SARS-CoV-2 infection induced higher titers of SARS-CoV-2 S-reactive IgG antibodies targeting both the S1 and S2 subunits, and concomitant IgM and IgA antibodies, lasting throughout the observation period. SARS-CoV-2-uninfected donor sera exhibited specific neutralizing activity against SARS-CoV-2 and SARS-CoV-2 S pseudotypes. Distinguishing preexisting and de novo immunity will be critical for our understanding of susceptibility to and the natural course of SARS-CoV-2 infection.