Anti-human leukocyte antigen and anti-ABO antibodies after SARS-CoV-2 mRNA vaccination in kidney transplant recipients.

INTRODUCTION: In this study, we evaluated whether SARS-CoV-2 mRNA vaccines induce anti-human leukocyte antigen (HLA) antibodies and anti- ABO blood type antibodies (ABOAb) in kidney transplant recipients (KTRs). METHODS: Sixty-three adult KTRs with functioning grafts who received two doses of the SARS-CoV-2 mRNA vaccine were enrolled in this cohort. Changes in anti-ABO blood type immunoglobulin IgM and IgG antibody titers, flow panel reactive antibody (PRA), de novo donor-specific anti-human leukocyte antigen antibodies (DSA), and kidney allograft function before and after vaccination were evaluated. RESULTS: Only one patient experienced conversion from negative to positive flow PRA after vaccination. However, there was no DSA in single antigen flow-bead assays. The mean fluorescence intensity (MFI) in the eight DSA-positive recipients did not significantly change before and after vaccination (p = .383), and no additional DSA was produced after vaccination in those patients. No significant elevation of ABOAb titer was observed for either IgM (p = .438) or IgG (p = .526) after vaccination. There was no significant deterioration in estimated glomerular filtration rate (eGFR) after vaccination (p = .877) or elevation of the urine protein-to-creatinine ratio (p = .209) after vaccination. One episode of AMR was observed in addition to a preexisting acute cellular rejection. CONCLUSIONS: The SARS-CoV-2 mRNA vaccine did not induce anti-HLA antibody or ABOAb production in KTRs.

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.

We evaluated the humoral and cellular immune responses and safety of the third severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine with a longer interval after the second vaccination in kidney transplant recipients (KTRs). We enrolled 54 kidney transplant recipients without a history of coronavirus disease 2019 (COVID-19), who received a third dose of the vaccine. We assessed anti-SARS-CoV-2 spike antibody and antigen-specific T cells using enzyme-linked immunospot (ELISpot) against the spike protein at baseline, after the second vaccination, and after the third vaccination. We also evaluated the adverse events related to each dose of the vaccine. The duration between the second and third vaccinations was 7 ± 1 month. All 17 (100%) KTRs with anti-SARS-CoV-2 antibody positivity after the second vaccination and 27 of 37 (73%) KTRs without anti-SARS-CoV-2 antibody positivity after the second vaccination were positive for anti-SARS-CoV-2 antibodies (p=0.022). Anti-SARS-CoV-2 antibody titers were significantly higher than those after the second vaccination (p<0.001). Age ≥ 60 years and lymphocyte count < 1150/mm3 were confirmed as risk factors for anti-SARS-CoV-2 antibody negativity after the third vaccination in multivariate regression analysis. ELISpot cytokine activities were positive after the third vaccination in 26 of 29 (90%) KTRs with ELISpot cytokine activity positivity after the second vaccination and 12 of 24 (50%) KTRs without ELISpot cytokine activity after the second vaccination. The rate of change in cytokine activity after the third vaccination was significantly higher than that after the second vaccination (p<0.001). Only lymphocyte counts less than 1150/mm3 were confirmed as risk factors for ELISpot cytokine activity negativity in the multivariate regression analysis. Systemic adverse events classified as greater than moderate did not differ for each vaccine dose. None of the patients showed clinical symptoms of acute rejection. The third SARS-CoV-2 mRNA vaccine administration, with a longer interval after the second vaccination, improved humoral and cellular immune responses to SARS-CoV-2 mRNA vaccines without severe adverse effects in the KTRs.

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

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.