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 - 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 - Publisher Copyright:
© 2024 The Author(s).
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.
UR - http://www.scopus.com/inward/record.url?scp=85210395290&partnerID=8YFLogxK
U2 - 10.1097/TP.0000000000005119
DO - 10.1097/TP.0000000000005119
M3 - Article
C2 - 38902860
AN - SCOPUS:85210395290
SN - 0041-1337
VL - 108
SP - 2420
EP - 2433
JO - Transplantation
JF - Transplantation
IS - 12
ER -