Potent induction of humoral and cellular immunity after bivalent BA.4-5 mRNA vaccination in dialysis patients
BRONDER S. 1, MIHM J. 2, URSCHEL R. 1, SCHMIDT T. 1, WIDERA M. 3, SESTER U. 2, SESTER M. 1
1 Department of Transplant and Infection Immunology, Saarland University, Campus, Homburg, Germany; 2 Department of Internal Medicine IV, SHG Kliniken, Völklingen, Germany; 3 Institute for Medical Virology, University Hospital Frankfurt, Goethe University , Frankfurt, Germany
Objectives: The risk of infection and severe COVID-19 disease with fatal outcome is increased in hemodialysis patients due to inadequate humoral and cellular immune responses. Until now, knowledge on immunogenicity of the bivalent Omicron BA.4-5 vaccine is limited. Therefore, vaccine-induced humoral and cellular immunity and the effect of a previous infection were comparatively analyzed in dialysis patients and immunocompetent controls.
Methods: Specific humoral and cellular immunity toward the spike protein derived from parental SARS-CoV-2 and Omicron VOCs BA.1, BA.2 and BA.4/5 were analyzed before and 13-18 days after vaccination in 33 patients and 58 age-matched controls. SARS-CoV-2-spike-specific IgGs were quantified by ELISA and their neutralizing ability by a micro-neutralization assay. Spike-specific CD4 and CD8 T-cells were characterized using flow cytometry.
Results: Both previously infected and non-infected dialysis patients showed a significant induction of IgG, neutralizing titers, CD4 and CD8 T-cell levels toward the parental spike protein after vaccination with no difference between the groups. However, infected patients had significantly higher spike-specific CD4 T-cell levels compared to infection-naïve patients (p=0.004). This was associated with a concomitantly lower expression of CTLA-4 in infected patients. Overall, vaccine-induced CD4 and CD8 T-cell levels towards all variants were similar indicating cross-reactivity (p<0.0001, r=0.93-0.97). Spike-specific CD4 T-cells were predominantly polyfunctional (IFNγ+IL-2+TNFα+), whereas CD8 T-cells were mostly IFNγ+TNFα+. Comparison of patients and controls revealed no difference in spike-specific IgG levels and CD8 T-cells. However, among infected individuals, patients had lower neutralizing activity and significantly higher spike-specific CD4 T-cells levels (p≤0.0005). Vaccination was well tolerated although local and/or systemic adverse events were reported more frequently in controls.
Conclusion: There was no evidence for an impaired vaccine-induced immunogenicity in dialysis patients. Unlike in controls, previous infection of patients was even associated with higher levels of spike-specific CD4 T-cells, which may reflect a more intense immunological imprinting after viral infection.