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 μM-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.

Microfluidic antibody profiling after repeated SARS-CoV-2 vaccination links antibody affinity and concentration to impaired immunity and variant escape in patients on anti-CD-20 therapy

“…Thus, MAAP may allow for a more granular assessment of antibody responses following antigen exposure and provide insights into the potency of the humoral response against emerging variants of concern. Nevertheless, a recent study exploring antibody profiles in pre-Omicron sera from largely immunocompetent patients with a variety of antigenic exposures to SARS-CoV-2 antigens (including after one or more doses of WT vaccine or after infection or both) showed similar antibody affinities against Omicron versus WT or Delta Spike antigens, albeit the timing of serum sampling for antibody assessment in this study was widely variable (28).…”

Continuous population-level monitoring of SARS-CoV-2 seroprevalence in a large European metropolitan region

“…Yet, these analyses are limited by the participation rate resulting in a relatively small sample size. Certain consequences of CoV2 infectionpotentially CoV2 clade dependent 20 may take more time to manifest and large numbers of patients may need to be assessed to perform solid statistical analyses due to the heterogeneous clinical picture 17,[69][70][71] and the phenotypic J o u r n a l P r e -p r o o f heterogeneity of post-acute COVID-19 sequalae 72 . Furthermore, it cannot be excluded that selection effects or potential residual confounding may have influenced the findings of the survey.…”

“…The absorbance at 450 nm was measured in a plate reader (Perkin Elmer, EnVision) and the inflection points of the sigmoidal binding curves were determined using the custom designed fitting algorithm described below. The secondary antibodies we have used were tested and validated previously 20 and replicability as well as influence of different sample types (e.g. serum and heparin plasma) on the TRABI have already been reported 17,20 .…”

“…The secondary antibodies we have used were tested and validated previously 20 and replicability as well as influence of different sample types (e.g. serum and heparin plasma) on the TRABI have already been reported 17,20 .…”

“…As waning of CoV2 antibodies has been reported in multiple instances [11][12][13][14][15] , single timepoint serology estimates may yield misleading insights into the true J o u r n a l P r e -p r o o f extent of CoV2 spread. We, therefore, aimed to investigate the evolution of the CoV2 seroprevalence in the canton of Zurich, a particularly low prevalence setting during the first and second waves in 2020, using an in-house developed tripartite automated blood immunoassay (TRABI) already employed in multiple studies [16][17][18][19][20] . Continuous immunosurveys were conducted in a large cohort of the University Hospital of Zurich (n=55'814 samples) and blood donors from the Blood Donation Services of the canton of Zurich (n=16'291), over a period from December 2019 to December 2020, i.e.…”