Predictors and Dynamics of the Humoral and Cellular Immune Response to SARS-CoV-2 mRNA Vaccines in Hemodialysis Patients: A Multicenter Observational Study
Authors: Van Praet Jens , Reynders Marijke , De Bacquer Dirk , Viaene Liesbeth , Schoutteten Melanie K. , Caluwé Rogier , Doubel Peter , Heylen Line , De Bel Annelies V. , Van Vlem Bruno , Steensels Deborah , De Vriese An S. 
Published: September 2021

Significance Statement
Patients on hemodialysis characteristically have an impaired response to vaccination. This large multicenter cohort study found an incomplete and delayed humoral and a blunted cellular immune response to SARS-CoV-2 vaccination in patients on hemodialysis. Recipients of the mRNA-1273 vaccine had mean responses that were substantially larger than responses of BNT162b2 vaccine recipients, and were significantly more likely to achieve the higher antibody thresholds thought to be required for preventing infection. A 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 humoral and cellular responses. The strikingly better responses in mRNA-1273 recipients may be related to the vaccine’s higher mRNA content, suggesting that a high-dose vaccine may help improve SARS-CoV-2 vaccine effectiveness in patients on hemodialysis.

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.