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

Abstract

IntroductionStudies 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.Materials and methodsTo 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 CXCL9 mRNA and de novo donor-specific antibodies (DSA). Secondary outcomes included development of anti-viral immune responses against the wild-type and Delta variant of SARS-CoV-2.ResultsAt a median of 85 days, no KTRs developed de novo DSAs and only one patient developed acute rejection following recent conversion to belatacept, which was associated with increased creatinine and urinary CXCL9 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.ConclusionsSARS-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.

SARS-CoV-2 mRNA vaccination is not associated with the induction of anti-HLA or non-HLA antibodies

“…At a median of 85 days after initial vaccination, none of the kidney transplant recipients had developed de novo anti-HLA antibodies. Only one patient developed a T-cell mediated rejection 40 days after initial vaccination, following conversion from Tacrolimus to Belatacept two days before vaccination [ 21 ]. Second, Sattler et al detected no de novo anti-HLA antibodies, no increase of existing anti-HLA antibodies and no cases of acute rejection after the second BNT162b2 vaccine dose [ 22 ].…”

Solid Organ Rejection following SARS-CoV-2 Vaccination or COVID-19 Infection: A Systematic Review and Meta-Analysis

“…Cells in the anterior chamber There were 42 case reports [5][6][7][8][11][12][13]17,18,[20][21][22][24][25][26][27][29][30][31][32][33][34][35][37][38][39][40][41][42][43][44][45][48][49][50][51][52][53][54][55][56][57], 8 case series [9,10,14,28,36,46,47,58] and 2 cohort studies [19,23]. These studies were conducted in t...…”

“…These studies were conducted in the United States (n = 14), India (n = 7), Italy (n = 5), Canada (n = 4), United Kingdom (n = 3), France (n = 3), Brazil (n = 2), Lebanon (n = 2), Australia (n = 1), Greece (n = 1), Egypt (n = 1), Denmark (n = 1), Japan (n = 1), Israel (n = 1), South Korea (n = 1), Slovakia (n = 1), Croatia (n = 1), China (n = 1), Mexico (n = 1) and Sweden (n = 1). The majority of the studies were single centre [5][6][7][8][9][11][12][13]17,18,[20][21][22][48][49][50][51][52][53][54][55][56][57][58], and only six studies were multi-centre [10,14,19,23,46,47]. The median NOS score for these studies was 6 (range, 5-7).…”

“…There were reports of fifty-six organ rejection cases following COVID-19 vaccination (fifty-one new-onset cases [5][6][7][8][9][39][40][41][42][43] and five relapsed cases [5,9,36,38]) (see Table 1). Allograft rejections after COVID-19 vaccination occurred for cornea (n = 38, 67.8%) [5,8,17,[20][21][22][23][24][28][29][30][31][32][33][34][35]37,38,42,43], liver (n = 11, 19.6%) [9,25,36,39,41], kidney (n = 6, 10.7%) [6,7,18,19,26,40] and pancreas (n = 1, 1.8%) [27] transplant recipients.…”

Tixagevimab/cilgavimab pre-exposure prophylaxis is associated with lower breakthrough infection risk in vaccinated solid organ transplant recipients during the Omicron wave

“…Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in solid organ transplant recipients (SOTRs) is associated with higher mortality compared to immunocompetent individuals. 1 Since antiviral responses to SARS-CoV-2 vaccines in SOTRs are attenuated, 2 additional strategies such as monoclonal antibody pre-exposure prophylaxis has been developed. 3 Tixagevimab and cilgavimab are neutralizing monoclonal antibodies directed against different epitopes of the receptor-binding domain of SARS-CoV-2 spike protein that have been associated with a lower risk of SARS-CoV-2 infection when used for pre-exposure prophylaxis in unvaccinated individuals.…”