Long-Term Immuno-Response and Risk of Breakthrough Infection After SARS-CoV-2 Vaccination in Kidney Transplantation

<b>Background</b>: Kidney transplant (KTx) recipients exhibit impaired responses to SARS-CoV-2 vaccination. Correlates of vaccine-induced immunity and risk factors for breakthrough infection are not fully defined. This study evaluated the humoral response trajectories and determinants of...

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Main Authors: Vincenzo Bellizzi, Mario Fordellone, Carmine Secondulfo, Paolo Chiodini, Giancarlo Bilancio
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Vaccines
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Online Access:https://www.mdpi.com/2076-393X/13/6/566
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author Vincenzo Bellizzi
Mario Fordellone
Carmine Secondulfo
Paolo Chiodini
Giancarlo Bilancio
author_facet Vincenzo Bellizzi
Mario Fordellone
Carmine Secondulfo
Paolo Chiodini
Giancarlo Bilancio
author_sort Vincenzo Bellizzi
collection DOAJ
description <b>Background</b>: Kidney transplant (KTx) recipients exhibit impaired responses to SARS-CoV-2 vaccination. Correlates of vaccine-induced immunity and risk factors for breakthrough infection are not fully defined. This study evaluated the humoral response trajectories and determinants of breakthrough infection in KTx recipients. <b>Methods</b>: KTx recipients received two doses of the BNT162b2 mRNA vaccine three weeks apart and a booster after six months. Patients were categorized based on pre-vaccination status: previous COVID-19 disease (DIS), asymptomatic SARS-CoV-2 infection (INF), or infection-naïve (NEG). Serum anti-spike antibody titers were assessed at baseline, before the second dose, and at 1, 3, 6, 9, and 12 months. Linear mixed models and survival analyses were performed. <b>Results</b>: Of 326 enrolled patients, 189 with complete time-point data were included in the longitudinal analysis. Antibodies were detectable in 89% of DIS/INF at baseline and 91% before the second dose, but were negligible in NEG. In NEG, the seropositivity increased after vaccination and booster, reaching 78% at 12 months. Age (−5% per year, <i>p</i> < 0.001) and BMI (+10% per unit, <i>p</i> = 0.004) influenced titers; antimetabolites and steroids had strong negative effects (−70%, <i>p</i> = 0.005; −84%, <i>p</i> = 0.001). Breakthrough infections occurred in 104 (31.9%); 40% were asymptomatic, and 2 patients died. An mTOR inhibitor was associated with a reduced infection risk (OR 0.27 [CI: 0.09–0.70], <i>p</i> = 0.009). Higher antibody titers correlated with delayed infection (<i>p</i> = 0.063). <b>Conclusions</b>: In KTx patients, humoral response to SARS-CoV-2 vaccination is limited in infection-naïve patients but improved by booster dosing; the hybrid immunity is more effective. Immunosuppressive regimens influence the immune response, and mTOR inhibitors may protect against breakthrough infection.
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spelling doaj-art-5d10e22f454e47459d313fba5b970f4c2025-08-20T03:26:56ZengMDPI AGVaccines2076-393X2025-05-0113656610.3390/vaccines13060566Long-Term Immuno-Response and Risk of Breakthrough Infection After SARS-CoV-2 Vaccination in Kidney TransplantationVincenzo Bellizzi0Mario Fordellone1Carmine Secondulfo2Paolo Chiodini3Giancarlo Bilancio4Division of Nephrology, Sant’Anna e San Sebastiano Hospital, 81100 Caserta, ItalyMedical Statistics Unit, University of Campania Luigi Vanvitelli, 80138 Naples, ItalyDepartment of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, ItalyMedical Statistics Unit, University of Campania Luigi Vanvitelli, 80138 Naples, ItalyDepartment of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, Italy<b>Background</b>: Kidney transplant (KTx) recipients exhibit impaired responses to SARS-CoV-2 vaccination. Correlates of vaccine-induced immunity and risk factors for breakthrough infection are not fully defined. This study evaluated the humoral response trajectories and determinants of breakthrough infection in KTx recipients. <b>Methods</b>: KTx recipients received two doses of the BNT162b2 mRNA vaccine three weeks apart and a booster after six months. Patients were categorized based on pre-vaccination status: previous COVID-19 disease (DIS), asymptomatic SARS-CoV-2 infection (INF), or infection-naïve (NEG). Serum anti-spike antibody titers were assessed at baseline, before the second dose, and at 1, 3, 6, 9, and 12 months. Linear mixed models and survival analyses were performed. <b>Results</b>: Of 326 enrolled patients, 189 with complete time-point data were included in the longitudinal analysis. Antibodies were detectable in 89% of DIS/INF at baseline and 91% before the second dose, but were negligible in NEG. In NEG, the seropositivity increased after vaccination and booster, reaching 78% at 12 months. Age (−5% per year, <i>p</i> < 0.001) and BMI (+10% per unit, <i>p</i> = 0.004) influenced titers; antimetabolites and steroids had strong negative effects (−70%, <i>p</i> = 0.005; −84%, <i>p</i> = 0.001). Breakthrough infections occurred in 104 (31.9%); 40% were asymptomatic, and 2 patients died. An mTOR inhibitor was associated with a reduced infection risk (OR 0.27 [CI: 0.09–0.70], <i>p</i> = 0.009). Higher antibody titers correlated with delayed infection (<i>p</i> = 0.063). <b>Conclusions</b>: In KTx patients, humoral response to SARS-CoV-2 vaccination is limited in infection-naïve patients but improved by booster dosing; the hybrid immunity is more effective. Immunosuppressive regimens influence the immune response, and mTOR inhibitors may protect against breakthrough infection.https://www.mdpi.com/2076-393X/13/6/566kidney transplantCOVIDSARS-CoV-2mRNA vaccineBNT162b2hybrid immunity
spellingShingle Vincenzo Bellizzi
Mario Fordellone
Carmine Secondulfo
Paolo Chiodini
Giancarlo Bilancio
Long-Term Immuno-Response and Risk of Breakthrough Infection After SARS-CoV-2 Vaccination in Kidney Transplantation
Vaccines
kidney transplant
COVID
SARS-CoV-2
mRNA vaccine
BNT162b2
hybrid immunity
title Long-Term Immuno-Response and Risk of Breakthrough Infection After SARS-CoV-2 Vaccination in Kidney Transplantation
title_full Long-Term Immuno-Response and Risk of Breakthrough Infection After SARS-CoV-2 Vaccination in Kidney Transplantation
title_fullStr Long-Term Immuno-Response and Risk of Breakthrough Infection After SARS-CoV-2 Vaccination in Kidney Transplantation
title_full_unstemmed Long-Term Immuno-Response and Risk of Breakthrough Infection After SARS-CoV-2 Vaccination in Kidney Transplantation
title_short Long-Term Immuno-Response and Risk of Breakthrough Infection After SARS-CoV-2 Vaccination in Kidney Transplantation
title_sort long term immuno response and risk of breakthrough infection after sars cov 2 vaccination in kidney transplantation
topic kidney transplant
COVID
SARS-CoV-2
mRNA vaccine
BNT162b2
hybrid immunity
url https://www.mdpi.com/2076-393X/13/6/566
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