TY - JOUR
T1 - Repeated COVID-19 Vaccination Drives Memory T- and B-cell Responses in Kidney Transplant Recipients
T2 - Results From a Multicenter Randomized Controlled Trial
AU - RECOVAC Consortium
AU - Malahe, S Reshwan K
AU - den Hartog, Yvette
AU - Rietdijk, Wim J R
AU - van Baarle, Debbie
AU - de Kuiper, Ronella
AU - Reijerkerk, Derek
AU - Ras, Alicia M
AU - Geers, Daryl
AU - Diavatopoulos, Dimitri A
AU - Messchendorp, A Lianne
AU - van der Molen, Renate G
AU - Imhof, Céline
AU - Frölke, Sophie C
AU - Bemelman, Frederike J
AU - Gansevoort, Ron T
AU - Hilbrands, Luuk B
AU - Sanders, Jan-Stephan F
AU - GeurtsvanKessel, Corine H
AU - Kho, Marcia M L
AU - de Vries, Rory D
AU - Reinders, Marlies E J
AU - Baan, Carla C
N1 - Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.
PY - 2024/12
Y1 - 2024/12
N2 - BACKGROUND: Insight into cellular immune responses to COVID-19 vaccinations is crucial for optimizing booster programs in kidney transplant recipients (KTRs).METHODS: In an immunologic substudy of a multicenter randomized controlled trial (NCT05030974) investigating different repeated vaccination strategies in KTR who showed poor serological responses after 2 or 3 doses of an messenger RNA (mRNA)-based vaccine, we compared SARS-CoV-2-specific interleukin-21 memory T-cell and B-cell responses by enzyme-linked immunosorbent spot (ELISpot) assays and serum IgG antibody levels. Patients were randomized to receive: a single dose of mRNA-1273 (100 μg, n = 25), a double dose of mRNA-1273 (2 × 100 μg, n = 25), or a single dose of adenovirus type 26 encoding the SARS-CoV-2 spike glycoprotein (Ad26.COV2.S) (n = 25). In parallel, we also examined responses in 50 KTR receiving 100 μg mRNA-1273, randomized to continue (n = 25) or discontinue (n = 25) mycophenolate mofetil/mycophenolic acid. As a reference, the data were compared with KTR who received 2 primary mRNA-1273 vaccinations.RESULTS: Repeated vaccination increased the seroconversion rate from 21% to 66% in all patients, which was strongly associated with enhanced levels of SARS-CoV-2-specific interleukin-21 memory T cells (odd ratio, 3.84 [1.89-7.78]; P < 0.001) and B cells (odd ratio, 35.93 [6.94-186.04]; P < 0.001). There were no significant differences observed in these responses among various vaccination strategies. In contrast to KTR vaccinated with 2 primary vaccinations, the number of antigen-specific memory B cells demonstrated potential for classifying seroconversion after repeated vaccination (area under the curve, 0.64; 95% confidence interval, 0.37-0.90; P = 0.26 and area under the curve, 0.95; confidence interval, 0.87-0.97; P < 0.0001, respectively).CONCLUSIONS: Our study emphasizes the importance of virus-specific memory T- and B-cell responses for comprehensive understanding of COVID-19 vaccine efficacy among KTR.
AB - BACKGROUND: Insight into cellular immune responses to COVID-19 vaccinations is crucial for optimizing booster programs in kidney transplant recipients (KTRs).METHODS: In an immunologic substudy of a multicenter randomized controlled trial (NCT05030974) investigating different repeated vaccination strategies in KTR who showed poor serological responses after 2 or 3 doses of an messenger RNA (mRNA)-based vaccine, we compared SARS-CoV-2-specific interleukin-21 memory T-cell and B-cell responses by enzyme-linked immunosorbent spot (ELISpot) assays and serum IgG antibody levels. Patients were randomized to receive: a single dose of mRNA-1273 (100 μg, n = 25), a double dose of mRNA-1273 (2 × 100 μg, n = 25), or a single dose of adenovirus type 26 encoding the SARS-CoV-2 spike glycoprotein (Ad26.COV2.S) (n = 25). In parallel, we also examined responses in 50 KTR receiving 100 μg mRNA-1273, randomized to continue (n = 25) or discontinue (n = 25) mycophenolate mofetil/mycophenolic acid. As a reference, the data were compared with KTR who received 2 primary mRNA-1273 vaccinations.RESULTS: Repeated vaccination increased the seroconversion rate from 21% to 66% in all patients, which was strongly associated with enhanced levels of SARS-CoV-2-specific interleukin-21 memory T cells (odd ratio, 3.84 [1.89-7.78]; P < 0.001) and B cells (odd ratio, 35.93 [6.94-186.04]; P < 0.001). There were no significant differences observed in these responses among various vaccination strategies. In contrast to KTR vaccinated with 2 primary vaccinations, the number of antigen-specific memory B cells demonstrated potential for classifying seroconversion after repeated vaccination (area under the curve, 0.64; 95% confidence interval, 0.37-0.90; P = 0.26 and area under the curve, 0.95; confidence interval, 0.87-0.97; P < 0.0001, respectively).CONCLUSIONS: Our study emphasizes the importance of virus-specific memory T- and B-cell responses for comprehensive understanding of COVID-19 vaccine efficacy among KTR.
U2 - 10.1097/TP.0000000000005119
DO - 10.1097/TP.0000000000005119
M3 - Article
C2 - 38902860
SN - 0041-1337
VL - 108
SP - 2420
EP - 2433
JO - Transplantation
JF - Transplantation
IS - 12
ER -