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

Kevin W. Ng(The Francis Crick Institute), Nikhil Faulkner(The Francis Crick Institute), Georgina H. Cornish(The Francis Crick Institute), Annachiara Rosa(The Francis Crick Institute), Ruth Harvey(The Francis Crick Institute), Saira Hussain(The Francis Crick Institute), Rachel Ulferts(The Francis Crick Institute), Christopher Earl(The Francis Crick Institute), Antoni G. Wrobel(The Francis Crick Institute), D.J. Benton(The Francis Crick Institute), Chloë Roustan(The Francis Crick Institute), William Bolland(The Francis Crick Institute), R. Houston Thompson(The Francis Crick Institute), Ana Agua‐Doce(The Francis Crick Institute), Philip Hobson(The Francis Crick Institute), Judith Heaney(University College London Hospitals NHS Foundation Trust), Hannah M. Rickman(University College London Hospitals NHS Foundation Trust), Stavroula Paraskevopoulou(University College London Hospitals NHS Foundation Trust), Catherine Houlihan(University College London Hospitals NHS Foundation Trust), Kirsty Thomson(University College London Hospitals NHS Foundation Trust), Emilie Sanchez(University College London Hospitals NHS Foundation Trust), Gee Yen Shin(University College London Hospitals NHS Foundation Trust), Moira Spyer(University College London Hospitals NHS Foundation Trust), Dhira Joshi(The Francis Crick Institute), Nicola O’Reilly(The Francis Crick Institute), P.A. Walker(The Francis Crick Institute), Svend Kjær(The Francis Crick Institute), Andrew Riddell(The Francis Crick Institute), Catherine Moore(University Hospital of Wales), Bethany R. Jebson(Great Ormond Street Hospital), Meredyth Wilkinson(Great Ormond Street Hospital), Lucy Marshall(Great Ormond Street Hospital), Elizabeth C. Rosser(Arthritis UK), Anna Radziszewska(Arthritis UK), Hannah Peckham(Arthritis UK), Coziana Ciurtin(Arthritis UK), Lucy R. Wedderburn(Great Ormond Street Hospital), Rupert Beale(The Francis Crick Institute), Charles Swanton(The Francis Crick Institute), Sonia Gandhi(The Francis Crick Institute), Brigitta Stockinger(The Francis Crick Institute), John W. McCauley(The Francis Crick Institute), S.J. Gamblin(The Francis Crick Institute), Laura E. McCoy(University College London), Peter Cherepanov(The Francis Crick Institute), Eleni Nastouli(University College London Hospitals NHS Foundation Trust), George Kassiotis(The Francis Crick Institute)
Science
November 6, 2020
10.1126/science.abe1107
Cited by 984Open Access
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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.

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