ABSTRACT
Background: Antiviral antibody responses to SARS-CoV-2 vaccines are reduced in kidney transplant recipients (KTRs) on belatacept compared to those not on belatacept. However, factors associated with lower odds of developing antibody responses in KTRs on belatacept are not known. Method(s): We conducted a retrospective multicenter cohort study of all KTRs on belatacept who received three mRNA vaccine doses at our institutions, where all KTRs on belatacept had anti-SARS-CoV-2 receptor-binding domain (RBD) antibodies measured by the Roche Elecsys immunoassay. The primary outcome was development of anti-RBD antibodies after the third vaccination. Result(s): 58 KTRs on belatacept were included. Median age was 62 and 69% were female. 78% were on prednisone, 60% on mycophenolate, 11% on mTOR inhibitors and 9% on azathioprine. After the third vaccine, 32/58 KTRs (55%) developed anti-RBD antibodies (Fig. 1A) with a median level of 3.3U/mL (Fig. 1B). Using univariate logistic regression, we found that age>=60, eGFR<45ml/min/1.73m2, prednisone use, and no prior SARS-CoV-2 infection were associated with significantly lower odds of developing anti-RBD responses after vaccination (Fig. 1C). These associations remained significant in the adjusted multivariable model (Fig. 1D). We also evaluated correlation between anti-RBD antibody levels and the number of days between vaccination and the most recent belatacept infusion for each vaccination but did not find an association between the two (Fig. 1E-G). Conclusion(s): Prednisone use, age>=60, eGFR<45ml/min/1.73m2, and no history of SARS-CoV-2 infection are associated with lower odds of anti-RBD antibody responses after vaccination in KTRs on belatacept.
ABSTRACT
Purpose: Emerging SARS-CoV-2 variants may be associated with a higher risk of breakthrough infections compared to wild-type (WT) virus in kidney transplant recipients (KTRs). The purpose of this study was to evaluate antiviral immune responses against WT and Delta (B.1.617.2) variant of SARS-CoV-2 after 3 doses of SARS-CoV-2 mRNA vaccines in KTRs. Method(s): We conducted a multicenter prospective cohort study of adult KTRs who received 3 doses of BNT162b2 or mRNA-1273. Blood samples were collected from KTRs before and 4 weeks after the 3rd vaccine dose. Sera from pre-pandemic healthy controls (HCs) and pre-pandemic kidney transplant control patients (KCs) were used for comparison. A Luminex-based multiplex assay was used to measure anti-spike antibodies for the WT, Alpha, Beta, Gamma and Delta variants of SARSCoV- 2. A surrogate virus neutralization test was used to assess neutralization against the WT and Delta variant. Patients were also monitored for rejection using several non-invasive biomarkers. Result(s): 54 KTRs were enrolled in the study. The median age was 63, 44% were female and the median time post-transplantation was 42 months. 94% received BNT162b2 vaccine. After the 3rd vaccine dose, there was a significant increase in anti-spike antibody MFIs against the WT, Alpha, Beta, Gamma and Delta variants (Fig. 1A, p<0.0001 for all). For comparison, all pre-pandemic HCs and KCs had a negative result for anti-spike antibody levels (Fig. 1B). Prior to the 3rd vaccine dose, 29% of KTRs had anti-spike antibodies against the WT compared to only 2% against the Delta variant (Fig. 1C, p=0.0001). After the 3rd vaccine dose, 67% of KTRs had anti-spike antibodies against the WT compared to 25% against the Delta variant (p<0.0001, Fig. 1D). Differences between WT and other variants are shown in Figure 1C-D. After the 3rd vaccine dose, there was a 2.1-fold and 2.5-fold increase in the percentage of KTRs with neutralizing responses against the WT and Delta variant respectively (p<0.0001 for both). There was no significant change in serum creatinine, proteinuria, or donor-derived cell-free DNA levels after vaccination. No episodes of rejection occurred during follow-up. Conclusion(s): Two doses of SARS-CoV-2 mRNA vaccines in KTRs are associated with minimal anti-spike antibody response directed against the Delta variant of SARS-CoV-2. After the third dose, a quarter of KTRs developed anti-spike antibodies directed against the Delta variant of SARS-CoV-2.
ABSTRACT
Background: There is limited data on the safety and efficacy of SARS-CoV-2 mRNA vaccines in kidney transplant recipients (KTRs). Methods: We conducted a prospective, multi-center study of 58 adult KTRs receiving mRNA-BNT162b2 or mRNA-1273 vaccines to assess vaccine safety and efficacy. Primary outcome was biopsy-proven rejection within 3 months of vaccination. Secondary outcomes included adverse events, serum creatinine, proteinuria, donor-derived cell-free DNA (ddcfDNA) levels, and antibody and cellular immunity generation against SARSCoV-2. Results: Median age was 62 with 41% females. Median time post-transplantation was 48 months. Only one patient (2%) developed acute cellular rejection though patient had been recently converted to belatacept. There were no severe adverse events or deaths during follow-up. Two patients (3%) developed SARS-CoV-2 infection, one of whom required hospitalization. There was no significant change in serum creatinine, proteinuria or ddcfDNA during the study. Following vaccination, 36%, 25% and 20% of KTRs developed anti-spike, anti-S1 and anti-RBD antibodies. KTRs on mycophenolate-based and steroid-maintenance regimens were less likely to develop an anti-spike antibody response. 100% of KTRs with anti-spike and anti-RBD antibodies had a neutralizing response, compared to 44% in KTRs with anti-spike but without anti-RBD antibodies (RR 2.25, 95% CI 1.08-4.67). There was a significant increase in IFN-gamma spots per 106 PBMCs incubated with S1 peptides following vaccination (p=0.0143). Conclusions: SARS-CoV-2 vaccination in KTRs was safe and associated with the generation of cellular immune response and in a third of patients with anti-spike antibody response. The degree of protection gained by these responses needs to be evaluated in future studies.