Impact of immunosuppressive treatment and type of SARS-CoV-2 vaccine on antibody levels after three vaccinations in patients with chronic kidney disease or kidney replacement therapy

Pim Bouwmans; A Lianne Messchendorp; Céline Imhof; Jan-Stephan F Sanders; Luuk B Hilbrands; Marlies E J Reinders; Priya Vart; Frederike J Bemelman; Alferso C Abrahams; René M A van den Dorpel; Marc A G J Ten Dam; Aiko P J de Vries; Theo Rispens; Maurice Steenhuis; Ron T Gansevoort; Marc H Hemmelder; RECOVAC Collaborators

doi:10.1093/ckj/sfac249

Impact of immunosuppressive treatment and type of SARS-CoV-2 vaccine on antibody levels after three vaccinations in patients with chronic kidney disease or kidney replacement therapy

Clin Kidney J. 2022 Nov 24;16(3):528-540. doi: 10.1093/ckj/sfac249. eCollection 2023 Mar.

Authors

Pim Bouwmans^{1

2}, A Lianne Messchendorp³, Céline Imhof³, Jan-Stephan F Sanders³, Luuk B Hilbrands⁴, Marlies E J Reinders⁵, Priya Vart^{6

7}, Frederike J Bemelman^{8

9}, Alferso C Abrahams¹⁰, René M A van den Dorpel¹¹, Marc A G J Ten Dam¹², Aiko P J de Vries^{13

14}, Theo Rispens^{15

16}, Maurice Steenhuis^{15

16}, Ron T Gansevoort³, Marc H Hemmelder^{1

2}; RECOVAC Collaborators

Affiliations

¹ Department of Internal Medicine, Division of Nephrology, Maastricht University Medical Center, Maastricht, The Netherlands.
² CARIM School for Cardiovascular Diseases, University of Maastricht, Maastricht, The Netherlands.
³ Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁴ Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands.
⁵ Department of Internal Medicine, Nephrology and Transplantation, Erasmus MC Transplant Institute, Erasmus Medical Center, Rotterdam, The Netherlands.
⁶ Department of Internal Medicine, University Medical Center Groningen, Groningen, The Netherlands.
⁷ Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, The Netherlands.
⁸ Amsterdam UMC Location University of Amsterdam, Renal Transplant Unit, Meibergdreef 9, Amsterdam, The Netherlands.
⁹ Amsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, The Netherlands.
¹⁰ Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
¹¹ Department of Nephrology, Maasstad Hospital, Rotterdam, The Netherlands.
¹² Department of Internal Medicine, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.
¹³ Department of Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
¹⁴ Leiden Transplant Center, Leiden, The Netherlands.
¹⁵ Department of Immunopathology, Sanquin Research, Amsterdam, The Netherlands.
¹⁶ Landsteiner Laboratory, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Abstract

Background: Patients with chronic kidney disease (CKD) or kidney replacement therapy demonstrate lower antibody levels after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination compared with healthy controls. In a prospective cohort, we analysed the impact of immunosuppressive treatment and type of vaccine on antibody levels after three SARS-CoV-2 vaccinations.

Methods: Control subjects (n = 186), patients with CKD G4/5 (n = 400), dialysis patients (n = 480) and kidney transplant recipients (KTR) (n = 2468) were vaccinated with either mRNA-1273 (Moderna), BNT162b2 (Pfizer-BioNTech) or AZD1222 (Oxford/AstraZeneca) in the Dutch SARS-CoV-2 vaccination programme. Third vaccination data were available in a subgroup of patients (n = 1829). Blood samples and questionnaires were obtained 1 month after the second and third vaccination. Primary endpoint was the antibody level in relation to immunosuppressive treatment and type of vaccine. Secondary endpoint was occurrence of adverse events after vaccination.

Results: Antibody levels after two and three vaccinations were lower in patients with CKD G4/5 and dialysis patients with immunosuppressive treatment compared with patients without immunosuppressive treatment. After two vaccinations, we observed lower antibody levels in KTR using mycophenolate mofetil (MMF) compared with KTR not using MMF [20 binding antibody unit (BAU)/mL (3-113) vs 340 BAU/mL (50-1492), P < .001]. Seroconversion was observed in 35% of KTR using MMF, compared with 75% of KTR not using MMF. Of the KTR who used MMF and did not seroconvert, eventually 46% seroconverted after a third vaccination. mRNA-1273 induces higher antibody levels as well as a higher frequency of adverse events compared with BNT162b2 in all patient groups.

Conclusions: Immunosuppressive treatment adversely affects the antibody levels after SARS-CoV-2 vaccination in patients with CKD G4/5, dialysis patients and KTR. mRNA-1273 vaccine induces a higher antibody level and higher frequency of adverse events.

Keywords: SARS-CoV-2 vaccination; antibody response; chronic kidney disease; dialysis; kidney transplantation.