Cellular and humoral response to SARS-CoV-2 vaccine BNT162b2 in adults with Chronic Kidney Disease G4/5

Abstract

The mRNA vaccines have proven to be very effective in preventing severe disease and death from SARS-CoV-2 in the general population. However, in patients with chronic kidney disease (CKD) in dialysis or with kidney transplants (KT) the vaccine responses vary, with severe breakthrough infections as a consequence. In this intervention study we investigated the magnitude and quality of the responses to mRNA vaccination administered prior to kidney replacement therapy (KRT). Twenty patients with CKD G4/5 and nine healthy controls were followed for 12 months after receiving two doses of BNT162b2 four weeks apart and a booster dose after 3-6 months. Induction of anti-Spike and anti-RBD IgG in plasma followed the same kinetics in CKD patients and controls, with a trend towards higher titers in controls. In accordance, there was no differences in the establishment of Spike-specific memory B-cells between groups. In contrast, the CKD patients showed lower levels of anti-Spike IgG in saliva and Spike-specific CD8⁺ T-cells in blood, possibly influencing the capacity of viral clearance which can contribute to an elevated risk of severe breakthrough infections. In conclusion, we found that CKD patients, despite having a reduced mucosal and cytotoxic immunity to BNT162b2, demonstrated a serological response in plasma similar to healthy controls. This suggests that immunization prior to RRT is efficient and motivated. (EudraCT-nr 2021-000988-68).

Keywords: COVID-19; Chronic kidney disease; Kidney failure; SARS-CoV-2; Vaccine.

Fig. 1

Study design. A. Protocol with interval for primary and booster vaccination with mRNA vaccine BNT162b2 and sampling (blood and saliva) of patients with chronic kidney disease (CKD) G4/5 prior to kidney replacement therapy and healthy controls. T0-time for first vaccine dose, T1 –second vaccine dose, T2-two weeks after the second dose, T3 two months after the second dose, T4-third vaccine dose, one to four months after the second dose, T5 – two weeks after the third dose, T6 – end of study, 12 months after the first dose. Between T5 and T6 some patients were given fourth vaccine dose outside the study B. Outcome of enrollment of participants.

Fig. 2

Antibody response following vaccination with mRNA BTN162b2 in patients with chronic kidney disease (CKD) G4/5 versus healthy controls. T0-T6 represent different time points. A. Individual production of anti-spike IgG plasma antibodies over time. B. Median anti-spike IgG plasma antibodies over time. Error bars with 95 % CI. C. Avidity of anti-spike IgG plasma antibodies measured as the proportion of remaining binding after chaotropic wash. D. Individual production of anti-receptor-binding domain (RBD) IgG plasma antibodies over time. E. Median anti-RBD IgG plasma antibodies over time. Error bars with 95 % CI. F.Comparison of anti-spike IgG plasma antibodies two weeks after the first booster dose (T5) in subject who became ill with COVID-19 in the time period between T5 and T6 versus subjects with no infection during the study period. Line represent median. G. Anti-spike IgG in saliva two weeks after the second dose (T2). Line represent median. H. Correlation between anti-spike IgG in plasma and in saliva two weeks after the second dose. LLOQ = lower limit of quantification. Statistic significant differences between groups marked with black asterisk, and within the group with respective color. *p < 0.05, **p < 0.01, ***p < 0.001 ns = not significant. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 3

Antigen specific memory B-cells (MBC) following vaccination with mRNA BTN162b2 in patients with chronic kidney disease (CKD) G4/5 versus healthy controls. T0-T6 represent different time points. A. Proportion of spike switched MBCs of total MBCs over time. B. Proportion of receptor-binding domain (RBD) switched MBC of total MBCs over time.Line, box and whiskers represent the median, interquartile range (IQR) and min-max range, respectively. Statistic significant differences between groups marked with black asterisk, and within the group with respective color. *p < 0.05, **p < 0.01, ***p < 0.001 ns = not significant. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 4

Antigen specific memory T-cells following vaccination with mRNA BTN162b2 in patients with chronic kidney disease (CKD) G4/5 versus healthy controls. T0-T6 represent different time points. A. Proportion of interferon gamma (IFNƴ) producing spike specific memory CD4⁺ T-cells of total memory CD4⁺ T-cells over time. B. Proportion of tumor necrosis factor (TNF) producing spike specific memory CD4⁺ T-cells of total memory CD4⁺ T-cells over time. C. Proportion of interleukin-2 (IL-2) producing spike specific memory CD4⁺ T-cells of total memory CD4⁺ T-cells over time D. Proportion of spike specific Th₁ (producing either IFNƴ or IL-2 or both) of total CD4⁺ cells over time. E. Proportion of IFNƴ producing spike specific memory CD8⁺ T-cells of total memory CD8⁺ T-cells over time. F. Proportion of TNF producing spike specific memory CD8⁺ T-cells of total memory CD8⁺ T-cells over time.Line, box and whiskers represent the median, interquartile range (IQR) and min-max range, respectively. Statistic significant differences between groups marked with black asterisk, and within the group with respective color. *p < 0.05, **p < 0.01, ***p < 0.001. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)