230.5: Antibody Response and Molecular Graft Surveillance in Kidney Transplant Recipients Following SARS-CoV-2 Vaccination

Introduction: Preliminary studies suggest that kidney transplant recipients (KTRs) show diminished humoral responses to SARS-CoV-2 vaccination. Although reports of allograft rejection around the time of SARS-CoV-2 vaccination have been rare, there is no recommended framework for monitoring for potential vaccine-related allograft injury. Here, we describe an approach for longitudinal assessment of immunogenicity and safety of SARS-COV-2 vaccination in KTRs. Methods: KTRs eligible for SARS-CoV-2 vaccination were identified through medical records, beginning March 12, 2021. Baseline and weekly blood samples were collected for routine assessment, SARS-CoV-2 spike protein antibody titers, dd-cfDNA (AlloSure, CareDx) and gene expression profiling (GEP) (AlloMap, CareDx) for 12 weeks. HLA DSA testing was performed at baseline, 2 weeks after completion of vaccine doses and at week 12. Antibody response was defined as a 10-fold increase in total binding IgG titers. Results: 49 KTRs were identified for analysis. Patient demographics are summarized in Table 1. 10 patients (20.4%) demonstrated a spike antibody response following completion of the vaccine series. Patients with a prior history of COVID-19 were more likely to mount a spike antibody response (n=8, 53.3%) compared to those with no reported history of COVID-19 (n=2, 5.8%). The odds ratio was 18.3 (95% CI 3.2, 105.0, p=0.0005). Median dd-cfDNA levels did not differ between pre- and post-vaccination (0.23% versus 0.21% respectively; Table 2). There was no significant difference between pre- and post-vaccination GEP scores (9.85 versus 10.4 respectively; Table 2). No patients developed clinically significant DSA, eGFR decline or allograft rejection following vaccination. Conclusions: Quantitative antibody responses were strongly associated with a diagnosis of prior SARS-CoV-2 infection. Stability of eGFR, dd-cfDNA, GEP profiles and lack of allosensitization reinforce the safety profile of SARS-CoV-2 vaccination in KTRs. Further studies are needed to better understand immunogenicity in SARS-CoV-2 naïve individuals, including whether cellular responses are protective in the absence of humoral responses.