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.