Both COVID-19 infection and vaccination induce high-affinity cross-clade responses to SARS-CoV-2 variants
Marc Emmenegger,
Sebastian Fiedler,
Silvio D. Brugger,
Sean R.A. Devenish,
Alexey S. Morgunov,
Alison Ilsley,
Francesco Ricci,
Anisa Y. Malik,
Thomas Scheier,
Leyla Batkitar,
Lidia Madrigal,
Marco Rossi,
Georg Meisl,
Andrew K. Lynn,
Lanja Saleh,
Arnold von Eckardstein,
Tuomas P.J. Knowles,
Adriano Aguzzi
Affiliations
Marc Emmenegger
Institute of Neuropathology, University of Zurich, 8091 Zurich, Switzerland; Corresponding author
Sebastian Fiedler
Fluidic Analytics, Unit A, The Paddocks Business Centre, Cherry Hinton Road, Cambridge CB1 8DH, UK
Silvio D. Brugger
Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
Sean R.A. Devenish
Fluidic Analytics, Unit A, The Paddocks Business Centre, Cherry Hinton Road, Cambridge CB1 8DH, UK
Alexey S. Morgunov
Fluidic Analytics, Unit A, The Paddocks Business Centre, Cherry Hinton Road, Cambridge CB1 8DH, UK; Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK
Alison Ilsley
Fluidic Analytics, Unit A, The Paddocks Business Centre, Cherry Hinton Road, Cambridge CB1 8DH, UK
Francesco Ricci
Fluidic Analytics, Unit A, The Paddocks Business Centre, Cherry Hinton Road, Cambridge CB1 8DH, UK
Anisa Y. Malik
Fluidic Analytics, Unit A, The Paddocks Business Centre, Cherry Hinton Road, Cambridge CB1 8DH, UK
Thomas Scheier
Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
Leyla Batkitar
Institute of Neuropathology, University of Zurich, 8091 Zurich, Switzerland
Lidia Madrigal
Institute of Neuropathology, University of Zurich, 8091 Zurich, Switzerland
Marco Rossi
Department of Laboratory Medicine, University Hospital Zürich, 8091 Zurich, Switzerland
Georg Meisl
Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK
Andrew K. Lynn
Fluidic Analytics, Unit A, The Paddocks Business Centre, Cherry Hinton Road, Cambridge CB1 8DH, UK
Lanja Saleh
Department of Laboratory Medicine, University Hospital Zürich, 8091 Zurich, Switzerland
Arnold von Eckardstein
Department of Laboratory Medicine, University Hospital Zürich, 8091 Zurich, Switzerland
Tuomas P.J. Knowles
Fluidic Analytics, Unit A, The Paddocks Business Centre, Cherry Hinton Road, Cambridge CB1 8DH, UK; Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK; Cavendish Laboratory, Department of Physics, University of Cambridge, JJ Thomson Ave, Cambridge CB3 0HE, UK
Adriano Aguzzi
Institute of Neuropathology, University of Zurich, 8091 Zurich, Switzerland; Corresponding author
Summary: The B.1.1.529 (omicron) variant has rapidly supplanted most other SARS-CoV-2 variants. Using microfluidics-based antibody affinity profiling (MAAP), we have characterized affinity and IgG concentration in the plasma of 39 individuals with multiple trajectories of SARS-CoV-2 infection and/or vaccination. Antibody affinity was similar against the wild-type, delta, and omicron variants (KA ranges: 122 ± 155, 159 ± 148, 211 ± 307 μM-1, respectively), indicating a surprisingly broad and mature cross-clade immune response. Postinfectious and vaccinated subjects showed different IgG profiles, with IgG3 (p-value = 0.002) against spike being more prominent in the former group. Lastly, we found that the ELISA titers correlated linearly with measured concentrations (R = 0.72) but not with affinity (R = 0.29). These findings suggest that the wild-type and delta spike induce a polyclonal immune response capable of binding the omicron spike with similar affinity. Changes in titers were primarily driven by antibody concentration, suggesting that B-cell expansion, rather than affinity maturation, dominated the response after infection or vaccination.
