Predictors and Dynamics of the Humoral and Cellular Immune Response to SARS-CoV-2 mRNA Vaccines in Hemodialysis Patients: A Multicenter Observational Study

Abstract

Background: Preliminary evidence suggests patients on hemodialysis have a blunted early serological response to SARS-CoV-2 vaccination. Optimizing the vaccination strategy in this population requires a thorough understanding of predictors and dynamics of humoral and cellular immune responses to different SARS-CoV-2 vaccines.

Methods: This prospective multicenter study of 543 patients on hemodialysis and 75 healthy volunteers evaluated the immune responses at 4 or 5 weeks and 8 or 9 weeks after administration of the BNT162b2 or mRNA-1273 vaccine, respectively. We assessed anti-SARS-CoV-2 spike antibodies and T cell responses by IFN-γ secretion of peripheral blood lymphocytes upon SARS-CoV-2 glycoprotein stimulation (QuantiFERON assay) and evaluated potential predictors of the responses.

Results: Compared with healthy volunteers, patients on hemodialysis had an incomplete, delayed humoral immune response and a blunted cellular immune response. Geometric mean antibody titers at both time points were significantly greater in patients vaccinated with mRNA-1273 versus BNT162b2, and a larger proportion of them achieved the threshold of 4160 AU/ml, corresponding with high neutralizing antibody titers in vitro (53.6% versus 31.8% at 8 or 9 weeks, P <0.0001). Patients vaccinated with mRNA-1273 versus BNT162b2 exhibited significantly greater median QuantiFERON responses at both time points, and a larger proportion achieved the threshold of 0.15 IU/ml (64.4% versus 46.9% at 8 or 9 weeks, P <0.0001). Multivariate analysis identified COVID-19 experience, vaccine type, use of immunosuppressive drugs, serum albumin, lymphocyte count, hepatitis B vaccine nonresponder status, and dialysis vintage as independent predictors of the humoral and cellular responses.

Conclusions: The mRNA-1273 vaccine's greater immunogenicity may be related to its higher mRNA dose. This suggests a high-dose vaccine might improve the impaired immune response to SARS-CoV-2 vaccination in patients on hemodialysis.

Graphical abstract

Figure 1.

Humoral immune response. (A) Geometric mean titers (95% confidence intervals) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antibody at week 4 and week 8 after BNT162b2 vaccination in patients on hemodialysis (red dashed line) and healthy volunteers (red solid line), and at week 5 and week 9 after mRNA-1273 vaccination in patients on hemodialysis (blue dashed line) and healthy volunteers (blue solid line). (B) Proportion of patients on hemodialysis and controls with SARS-CoV-2 spike antibody levels within a given range 4 or 5 weeks and 8 or 9 weeks after BNT162b2 or mRNA-1273 vaccination.

Figure 2.

Cellular response. Median (interquartile range) QuantiFERON response to antigen 2 at week 4 and week 8 after BNT162b2 vaccination in patients on hemodialysis (red dashed line) and healthy volunteers (red solid line) and at week 5 and week 9 after mRNA-1273 vaccination in patients on hemodialysis (blue dashed line) and healthy volunteers (blue solid line).

Figure 3.

Correlation between the humoral and cellular immune response. Correlation between SARS-CoV-2 spike antibody titers and QuantiFERON at week 8 or 9 in patients on hemodialysis (blue) and healthy volunteers (red). The dashed lines represent the cutoffs of 4160 AU/ml and 0.15 IU/ml, respectively. The threshold of 4160 AU/ml corresponds with a 95% probability of high neutralizing antibody titer (PRNT50 at a 1:250 dilution).

Figure 4.

Frequency of local and systemic solicited side effects. Relative frequency of solicited local and systemic reactions for 7 days after each vaccine dose in the hemodialysis group for the BNT162b2 (A) and mRNA-1273 vaccine (C), and the control group for the BNT162b2 (B) and mRNA-1273 vaccine (D). The panels show the combined postvaccination 1 and postvaccination 2 periods, with the proportion of participants that reported the side effect in one of both periods displayed in brown and the proportion of participants that reported the same side effect in both periods displayed in red.