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

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 recently shown that current therapeutic monoclonal antibodies exhibit a drastic loss of affinity against omicron. Here, we have characterized affinity and IgG concentration in the plasma of 39 individuals with multiple trajectories of SARS-CoV-2 infection and/or vaccination as well as in 2 subjects without vaccination or infection. Antibody affinity in patient plasma samples was similar against the wild-type, delta, and omicron variants (KA ranges 122{+/-}155, 159{+/-}148, 211{+/-}307 M-1, respectively), indicating a surprisingly broad and mature cross-clade immune response. We then determined the antibody iso- and subtypes against multiple SARS-CoV-2 spike domains and nucleoprotein. Postinfectious and vaccinated subjects showed different profiles, with IgG3 (p = 0.002) but not IgG1, IgG2 or IgG4 subtypes against the spike ectodomain being more prominent in the former group. Lastly, we found that the ELISA titers against the wildtype, delta, and omicron RBD variants correlated linearly with measured IgG concentrations (R=0.72) but not with affinity (R=0.29). These findings suggest that the wild-type and delta spike proteins 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.