Immunogenicity and safety of two doses of SARS‐CoV‐2 mRNA vaccine in kidney transplant recipients with low‐dose rituximab

Abstract

Objectives We evaluated whether the treatment history of low‐dose rituximab affected safety profiles, and humoral and cellular responses induced by severe acute respiratory syndrome coronavirus 2 messenger ribonucleic acid vaccine in healthy controls and kidney transplant recipients. Methods We enrolled 10 healthcare workers as controls, 22 kidney transplant recipients with rituximab, and 36 kidney transplant recipients without rituximab without history of coronavirus disease 2019 who received two doses of vaccine. We assessed anti‐severe acute respiratory syndrome coronavirus 2 spike antibody and the antigen‐specific T cells using enzyme‐linked immunospot against spike protein at baseline and after two doses of vaccine. Results All controls showed anti‐severe acute respiratory syndrome coronavirus 2 antibody seroconversion and enzyme‐linked immunospot positivity. Only 19/58 (33%) kidney transplant recipients experienced anti‐severe acute respiratory syndrome coronavirus 2 antibody seroconversion and 31/58 (53%) kidney transplant recipients developed enzyme‐linked immunospot assay positivity after vaccination. The anti‐severe acute respiratory syndrome coronavirus 2 antibody seroconversion rate and enzyme‐linked immunospot assay positivity rate after vaccination were not significantly different between kidney transplant recipients with or without rituximab. Multivariate regression analysis demonstrated rituximab was not associated with a lack of humoral and cellular responses to the vaccine. Conclusions Low‐dose rituximab in kidney transplant recipients did not affect humoral or cellular responses to the severe acute respiratory syndrome coronavirus 2 messenger ribonucleic acid vaccine without severe systemic adverse events including the deterioration of kidney function.

Humoral and cellular immune response and the safety of third SARS-CoV-2 mRNA vaccine with longer interval after the second vaccination in kidney transplant recipients

“…In previous studies, immunosuppressants, including steroids, MMF, belatacept, and triple immunosuppression; elderly patients; short period from transplantation; low lymphocyte counts; and low allograft function were confirmed as risk factors for negative immunogenicity after the third vaccination ( 8 , 10 – 15 ). Age > 60 years, low lymphocyte counts, and transplantation within 2 years were identified as risk factors in our study; however, immunosuppressants, including MMF, did not affect the anti-SARS-CoV-2 antibody positivity rate in our study, even though MMF was confirmed as a risk factor for a negative humoral response after the second SARS-CoV-2 mRNA vaccine in our previous study ( 16 ). MMF did not affect the seropositivity rate; however, the anti-SARS-CoV-2 antibody titer was significantly lower in KTRs with MMF.…”

“…Of the 58 KTRs who were enrolled in a study that evaluated the immunogenicity of two doses of SARS-CoV-2 mRNA in KTRs at our department, 54 KTRs were enrolled in this study ( 16 ). All participants completed three doses of the SARS-CoV-2 mRNA-1273 vaccine (Moderna) or BNT162b2 SARS-CoV-2 mRNA vaccine (Pfizer-BioNTech) between January and June 2022.…”

“…To analyze cellular responses, an ELISpot assay measuring interferon-gamma produced by specific SARS-CoV-2 T cells was performed as previously described ( 16 ). Briefly, PBMCs were isolated by specific gravity centrifugation using Ficall-Paque Premium (Cytiva, Tokyo, Japan), and cryopreserved until analysis.…”

“…ELISpot analysis was performed using an ELISpot Reader (Autoimmun Diagnostika; Strasberg, Germany). Cytokine activity was calculated from spot size and intensity values, as previously described ( 16 , 17 ). The rate of change in cytokine activity in each test was calculated using the formula below, and the mean value of the two measurements was used as the measured value.…”

“…The cut-off value was determined by calculating the mean ± 2 standard deviations in a group of healthcare workers obtained prior to the first vaccination in our previous study, and was determined as the rate of change in cytokine activity greater than 164 ( 16 ).…”