FUNCTIONALLY IMPAIRED ANTIBODY RESPONSE TO BNT162B2 BOOSTER VACCINATION IN CVID IgG RESPONDERS

Abstract

Background

While previous studies described the production of IgG-antibodies in a subgroup of CVID-patients following mRNA-vaccinations with bnt162b2 SARS-CoV2 (CVID responders), the functionality of these antibodies in terms of avidity as measured by the dissociation rate constant (k _dis) and the antibody response to booster immunization has not been studied.

Objective

In CVID responders and healthy individuals the avidity of anti-SARS-CoV-2 serum-antibodies and their neutralization capacity as measured by surrogate virus neutralizing antibodies were analyzed in addition to IgG-, IgM- and IgA-antibody levels and the response of circulating follicular T-helper cells after a third vaccination with BNT162b2 SARS-CoV2 mRNA-vaccine.

Methods

Binding IgG, IgA and IgM serum levels were analyzed by ELISA in CVID-patients responding to the primary vaccination (CVID responders, n=10) and healthy controls (n=41). The binding-avidity of anti-spike antibodies was investigated using biolayer interferometry in combination with biotin-labelled receptor-binding-domain (RBD) of SARS-CoV2 spike-protein and streptavidin-labelled sensors. Antigen-specific recall T-cell responses were assessed by measuring activation-induced markers by flow cytometry.

Results

After the third vaccination with BNT162b2 IgG-, IgM and IgA-antibody levels, sVNT levels and antibody avidity were lower in CVID responders as compared to healthy. In contrast αSpike-avidity was comparable in CVID responders and healthy individuals following primary vaccination. Follicular T-helper cell response to booster vaccination in CVID-responders was significantly reduced when compared to healthy individuals.

Conclusion

Impaired affinity-maturation during booster-response provides new insight into CVID pathophysiology.