Jan Stephan F Sanders1, A Lianne Messchendorp1, Rory D de Vries2, Carla C Baan3, Debbie van Baarle4,5, Rob van Binnendijk5, Dimitri A Diavatopoulos6,7, Daryl Geers2, Katharina S Schmitz2, Corine H Geurts van Kessel2, Gerco den Hartog5, Marcia Ml Kho3, Marion Pg Koopmans2, Renate G van der Molen7, Ester Bm Remmerswaal8, Nynke Rots5, Ron T Gansevoort1, Frederike J Bemelman9, Luuk B Hilbrands10, Marlies Ej Reinders3. 1. Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. 2. Department Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands. 3. Department of Internal Medicine, Nephrology and Transplantation, Erasmus MC Transplant Institute, Erasmus Medical Center, Rotterdam, The Netherlands. 4. Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, Groningen, The Netherlands. 5. Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands. 6. Radboud Center for Infectious Diseases, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands. 7. Radboud Institute for Molecular Life Sciences, Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands. 8. Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. 9. Renal Transplant Unit, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. 10. Department of Nephrology, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
Abstract
BACKGROUND: The immune response to COVID-19 vaccination is inferior in kidney transplant recipients (KTR), and to a lesser extent in patients on dialysis or with chronic kidney disease (CKD). We assessed the immune response 6 months after mRNA-1273 vaccination in kidney patients and compared this to controls. METHODS: 152 participants with CKD stages G4/5 (eGFR <30 mL/min/1.73m2), 145 participants on dialysis, 267 KTR, and 181 controls were included. SARS-CoV-2 Spike S1-specific IgG antibodies were measured by fluorescent bead-based multiplex-immunoassay, neutralizing antibodies to ancestral, Delta and Omicron (BA.1) variants by plaque reduction, and T-cell responses by IFN-γ release assay. RESULTS: At 6 months after vaccination S1-specific antibodies were detected in 100% of controls, 98.7% of CKD G4/5 patients, 95.1% of dialysis patients, and 56.6% of KTR. These figures were comparable to the response rates at 28 days, but antibody levels waned significantly. Neutralization of the ancestral and Delta variant was detected in most participants, whereas neutralization of Omicron was mostly absent. S-specific T-cell responses were detected 6 months in 75.0% of controls, 69.4% of CKD G4/5 patients, 52.6% of dialysis patients, and 12.9% of KTR. T-cell responses at 6 months were significantly lower than responses at 28 days. CONCLUSIONS: Although seropositivity rates at 6 months were comparable to that at 28 days after vaccination, significantly decreased antibody levels and T-cell responses were observed. The combination of low antibody levels, reduced T-cell responses, and absent neutralization of the newly-emerging variants indicates the need for additional boosts or alternative vaccination strategies in KTR.
BACKGROUND: The immune response to COVID-19 vaccination is inferior in kidney transplant recipients (KTR), and to a lesser extent in patients on dialysis or with chronic kidney disease (CKD). We assessed the immune response 6 months after mRNA-1273 vaccination in kidney patients and compared this to controls. METHODS: 152 participants with CKD stages G4/5 (eGFR <30 mL/min/1.73m2), 145 participants on dialysis, 267 KTR, and 181 controls were included. SARS-CoV-2 Spike S1-specific IgG antibodies were measured by fluorescent bead-based multiplex-immunoassay, neutralizing antibodies to ancestral, Delta and Omicron (BA.1) variants by plaque reduction, and T-cell responses by IFN-γ release assay. RESULTS: At 6 months after vaccination S1-specific antibodies were detected in 100% of controls, 98.7% of CKD G4/5 patients, 95.1% of dialysis patients, and 56.6% of KTR. These figures were comparable to the response rates at 28 days, but antibody levels waned significantly. Neutralization of the ancestral and Delta variant was detected in most participants, whereas neutralization of Omicron was mostly absent. S-specific T-cell responses were detected 6 months in 75.0% of controls, 69.4% of CKD G4/5 patients, 52.6% of dialysis patients, and 12.9% of KTR. T-cell responses at 6 months were significantly lower than responses at 28 days. CONCLUSIONS: Although seropositivity rates at 6 months were comparable to that at 28 days after vaccination, significantly decreased antibody levels and T-cell responses were observed. The combination of low antibody levels, reduced T-cell responses, and absent neutralization of the newly-emerging variants indicates the need for additional boosts or alternative vaccination strategies in KTR.