AUTHOR=Al Jurdi Ayman , Gassen Rodrigo B. , Borges Thiago J. , Solhjou Zhabiz , Hullekes Frank E. , Lape Isadora T. , Efe Orhan , Alghamdi Areej , Patel Poojan , Choi John Y. , Mohammed Mostafa T. , Bohan Brigid , Pattanayak Vikram , Rosales Ivy , Cravedi Paolo , Kotton Camille N. , Azzi Jamil R. , Riella Leonardo V. 

TITLE=Non-Invasive Monitoring for Rejection in Kidney Transplant Recipients After SARS-CoV-2 mRNA Vaccination

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.838985

DOI=10.3389/fimmu.2022.838985

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>Studies have shown reduced antiviral responses in kidney transplant recipients (KTRs) following SARS-CoV-2 mRNA vaccination, but data on post-vaccination alloimmune responses and antiviral responses against the Delta (B.1.617.2) variant are limited.</p></sec><sec><title>Materials and methods</title><p>To address this issue, we conducted a prospective, multi-center study of 58 adult KTRs receiving mRNA-BNT162b2 or mRNA-1273 vaccines. We used multiple complementary non-invasive biomarkers for rejection monitoring including serum creatinine, proteinuria, donor-derived cell-free DNA, peripheral blood gene expression profile (PBGEP), urinary <italic>CXCL9</italic> mRNA and <italic>de novo</italic> donor-specific antibodies (DSA). Secondary outcomes included development of anti-viral immune responses against the wild-type and Delta variant of SARS-CoV-2.</p></sec><sec><title>Results</title><p>At a median of 85 days, no KTRs developed <italic>de novo</italic> DSAs and only one patient developed acute rejection following recent conversion to belatacept, which was associated with increased creatinine and urinary <italic>CXCL9</italic> levels. During follow-up, there were no significant changes in proteinuria, donor-derived cell-free DNA levels or PBGEP. 36% of KTRs in our cohort developed anti-wild-type spike antibodies, 75% and 55% of whom had neutralizing responses against wild-type and Delta variants respectively. A cellular response against wild-type S1, measured by interferon-γ-ELISpot assay, developed in 38% of KTRs. Cellular responses did not differ in KTRs with or without antibody responses.</p></sec><sec><title>Conclusions</title><p>SARS-CoV-2 mRNA vaccination in KTRs did not elicit a significant alloimmune response. About half of KTRs who develop anti-wild-type spike antibodies after two mRNA vaccine doses have neutralizing responses against the Delta variant. There was no association between anti-viral humoral and cellular responses.</p></sec>