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

doi:10.1016/j.isci.2022.104766

Both COVID-19 infection and vaccination induce high-affinity cross-clade responses to SARS-CoV-2 variants

iScience. 2022 Aug 19;25(8):104766. doi: 10.1016/j.isci.2022.104766. Epub 2022 Jul 16.

Authors

Marc Emmenegger¹, Sebastian Fiedler², Silvio D Brugger³, Sean R A Devenish², Alexey S Morgunov^{2

4}, Alison Ilsley², Francesco Ricci², Anisa Y Malik², Thomas Scheier³, Leyla Batkitar¹, Lidia Madrigal¹, Marco Rossi⁵, Georg Meisl⁴, Andrew K Lynn², Lanja Saleh⁵, Arnold von Eckardstein⁵, Tuomas P J Knowles^{2

4

6}, Adriano Aguzzi¹

Affiliations

¹ Institute of Neuropathology, University of Zurich, 8091 Zurich, Switzerland.
² Fluidic Analytics, Unit A, The Paddocks Business Centre, Cherry Hinton Road, Cambridge CB1 8DH, UK.
³ Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
⁴ Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
⁵ Department of Laboratory Medicine, University Hospital Zürich, 8091 Zurich, Switzerland.
⁶ Cavendish Laboratory, Department of Physics, University of Cambridge, JJ Thomson Ave, Cambridge CB3 0HE, UK.

Abstract

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 (K _A 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.

Keywords: Disease; Immune response; Virology.