Diminishing Immune Responses against Variants of Concern in Dialysis Patients 4 Months after SARS-CoV-2 mRNA Vaccination

Abstract

Patients undergoing chronic hemodialysis were among the first to receive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations because of their increased risk for severe coronavirus disease and high case-fatality rates. By using a previously reported cohort from Germany of at-risk hemodialysis patients and healthy donors, where antibody responses were examined 3 weeks after the second vaccination, we assessed systemic cellular and humoral immune responses in serum and saliva 4 months after vaccination with the Pfizer-BioNTech BNT162b2 vaccine using an interferon-γ release assay and multiplex-based IgG measurements. We further compared neutralization capacity of vaccination-induced IgG against 4 SARS-CoV-2 variants of concern (Alpha, Beta, Gamma, and Delta) by angiotensin-converting enzyme 2 receptor-binding domain competition assay. Sixteen weeks after second vaccination, compared with 3 weeks after, cellular and humoral responses against the original SARS-CoV-2 isolate and variants of concern were substantially reduced. Some dialysis patients even had no detectable B- or T-cell responses.

Keywords: COVID-19; SARS-CoV-2; booster dose; coronavirus disease; dialysis; immunocompromised; longevity of immune response; mRNA vaccination; respiratory infections; severe acute respiratory syndrome coronavirus 2; vaccine-preventable diseases; variants of concern; viruses; zoonoses.

Figure 1

Significant decrease in humoral and cellular responses induced by Pfizer-BioNTech vaccine BNT162b2 (https://www.pfizer.com) against SARS-CoV-2 from 3 weeks to 16 weeks after second vaccination, observed in a study of immune response against variants of concern in dialysis patients 4 months after SARS-CoV-2 mRNA vaccination. A) IgG response in plasma; B) IgG response in saliva; C) neutralizing capacity toward SARS-CoV-2 wild type B.1; D) T-cell response measured by IFN-γ release assay. Blue circles indicate dialysis patients (n = 76) and red circles controls (n = 23). Samples were taken 3 weeks (T1) and 16 weeks (T2) after vaccination. Saliva (panel B) has reduced sample numbers in both groups because of issues in sample collection (T1 control, n = 22; T1 dialysis, n = 69; T2 control, n = 23; T2 dialysis. n = 71). T1 timepoint data has been published previously (13) and is reproduced here for clarity. Horizontal lines within boxes indicate medians; box tops and bottoms indicate the 25th and 75th percentiles; whiskers show the largest and smallest nonoutlier values. Outliers were determined by 1.5 times interquartile range. Statistical significance was calculated by Wilcoxon matched-pairs signed rank test when comparing T1 and T, and 2-sided Mann–Whitney–U test when comparing control and dialysis groups. ACE2, angiotensin-converting enzyme 2; IFN-γ, interferon γ; MFI; median fluorescence intensity; NS, not significant; RBD, receptor-binding domain; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; T1, timepoint 1; T2, timepoint 2.

Figure 2

Reduced neutralizing capacity against SARS-CoV-2 variants of concern observed in a study of immune response against variants of concern in dialysis patients 4 months after SARS-CoV-2 mRNA vaccination. Neutralizing capacity of plasma IgG toward SARS-CoV-2 variants of concern Alpha (A), Beta (B), and Gamma and Delta (C) in the dialysis (blue circles, n = 76) and control (red circles, n = 23) groups 16 weeks after second vaccination with Pfizer-BioNTech vaccine BNT162b2 (https://www.pfizer.com). Neutralization capacity is displayed as ratio, where 1 indicates maximum neutralization and 0 no neutralization. Horizontal lines within boxes indicate medians; box tops and bottoms indicate the 25th and 75th percentiles; whiskers show the largest and smallest nonoutlier values. Outliers were determined by 1.5 times interquartile range. Statistical significance was calculated by 2-sided Mann–Whitney–U test. ACE2, angiotensin-converting enzyme 2; NS, not significant; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; T1, timepoint 1; T2, timepoint 2.