Kinetics of immune responses elicited after three mRNA COVID-19 vaccine doses in predominantly antibody-deficient individuals.

Abstract Purpose Mass vaccination campaigns have reduced the incidence and severity of COVID-19. However, there is limited information about how patients with predominantly antibody-deficiencies (PAD) respond to COVID-19 vaccination. Here, we evaluated humoral and cellular responses developed in SARS-CoV-2-naïve PAD individuals after three mRNA-1273 vaccine doses. Methods Patients and healthy controls (HCs) were immunized at week 0 (w0) and w4. PAD individuals received an additional dose at w24. Blood samples were collected at w0, w4, w8, w24, and/or w28. We determined levels of anti-Spike and anti-RBD antibodies, Spike-specific IgG avidity, and neutralizing activity (Wuhan-Hu-1, Delta, and Omicron variants). Cellular responses were evaluated by IFN-γ ELISpot and flow cytometry. Results Unclassified primary antibody-deficiency patients (unPAD, n = 9) and HCs developed comparable vaccine-induced humoral responses. However, common variable immunodeficiency patients (CVID, n = 12) showed lower antibody responses than HCs. While the frequency of Spike-specific CD4 + T cells was similar between PAD patients and HCs, CD8 + T cells responses were reduced in CVID individuals. Both PAD groups showed lower levels of Spike-specific IFN-γ-producing T-cells. Combined immunodeficiency (CID, n = 1) and thymoma with immunodeficiency (TID, n = 1) patients developed cellular but not humoral responses after two immunizations. The third vaccine dose boosted humoral responses in most PAD patients, but had little effect on cellular immunity. Conclusion mRNA-1273 vaccine-induced immune responses in PAD individuals are heterogeneous, depend on the type and degree of antibody-deficiency, and should be immunomonitored to define a personalized vaccination strategy.