Pre-existing and de novo humoral immunity to SARS-CoV-2 in humans

• DOI: 10.1101/2020.05.14.095414
• Publication Date: 2020-05-16T03:55:11Z
• Authors: Kevin W. Ng; Nikhil Faulkner; Georgina H. Cornish; Annachiara Rosa; Ruth Harvey; Saira Hussain; Rachel Ulferts; Christopher Earl; Antoni Wrobel; Donald Benton; Chloe Roustan; William Bolland; Rachael Thompson; Ana Agua-Doce; Philip Hobson; Judith Heaney; Hannah Rickman; Stavroula Paraske...; Catherine F. Houl...; Kirsty Thomson; Emilie Sanchez; David Brealey; Gee Yen Shin; Moira J. Spyer; Dhira Joshi; Nicola O’Reilly; Philip A. Walker; Svend Kjaer; Andrew Riddell; Catherine Moore; Bethany R. Jebson; Meredyth G.Ll. Wi...; Lucy R. Marshall; Elizabeth C. Rosser; Anna Radziszewska; Hannah Peckham; Coziana Ciurtin; Lucy R. Wedderburn; Rupert Beale; Charles Swanton; Sonia Gandhi; Brigitta Stockinger; John McCauley; Steve Gamblin; Laura E. McCoy; Peter Cherepanov; Eleni Nastouli; George Kassiotis
• Keywords: Adult; Male; 0301 basic medicine; 570; General Science & Technology; 610; Antibodies, Viral; Viral Zoonoses; Antibodies; Young Adult; 03 medical and health sciences; 80 and over; Animals; Humans; Viral; Amino Acid Sequence; Aged; Aged, 80 and over; Multidisciplinary; Science & Technology; SARS-CoV-2; Immunity; Humoral; COVID-19; Middle Aged; Spike Glycoprotein; Immunity, Humoral; Immunoglobulin A; 3. Good health; Coronavirus; Multidisciplinary Sciences; HEK293 Cells; Immunoglobulin M; Immunoglobulin G; Spike Glycoprotein, Coronavirus; Science & Technology - Other Topics; Female; Epitope Mapping; Reports

AbstractSeveral related human coronaviruses (HCoVs) are endemic in the human population, causing mild respiratory infections1. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiologic agent of Coronavirus disease 2019 (COVID-19), is a recent zoonotic infection that has quickly reached pandemic proportions2,3. Zoonotic introduction of novel coronaviruses is thought to occur in the absence of pre-existing immunity in the target human population. Using diverse assays for detection of antibodies reactive with the SARS-CoV-2 spike (S) glycoprotein, we demonstrate the presence of pre-existing humoral immunity in uninfected and unexposed humans to the new coronavirus. SARS-CoV-2 S-reactive antibodies were readily detectable by a sensitive flow cytometry-based method in SARS-CoV-2-uninfected individuals and were particularly prevalent in children and adolescents. These were predominantly of the IgG class and targeted the S2 subunit. In contrast, SARS-CoV-2 infection induced higher titres of SARS-CoV-2 S-reactive IgG antibodies, targeting both the S1 and S2 subunits, as well as concomitant IgM and IgA antibodies, lasting throughout the observation period of 6 weeks since symptoms onset. SARS-CoV-2-uninfected donor sera also variably reacted with SARS-CoV-2 S and nucleoprotein (N), but not with the S1 subunit or the receptor binding domain (RBD) of S on standard enzyme immunoassays. Notably, SARS-CoV-2-uninfected donor sera exhibited specific neutralising activity against SARS-CoV-2 and SARS-CoV-2 S pseudotypes, according to levels of SARS-CoV-2 S-binding IgG and with efficiencies comparable to those of COVID-19 patient sera. Distinguishing pre-existing and de novo antibody responses to SARS-CoV-2 will be critical for our understanding of susceptibility to and the natural course of SARS-CoV-2 infection.