Repeated COVID-19 Vaccination Drives Memory T- and B-cell Responses in Kidney Transplant Recipients: Results From a Multicenter Randomized Controlled Trial

S. Reshwan K. Malahe*, Yvette Den Hartog, Wim J.R. Rietdijk, Debbie Van Baarle, Ronella De Kuiper, Derek Reijerkerk, Alicia M. Ras, Daryl Geers, Dimitri A. Diavatopoulos, A. Lianne Messchendorp, Renate G. Van Der Molen, Céline Imhof, Sophie C. Frölke, Frederike J. Bemelman, Ron T. Gansevoort, Luuk B. Hilbrands, Jan Stephan F. Sanders, Corine H. Geurtsvankessel, Marcia M.L. Kho, Rory D. De VriesMarlies E.J. Reinders, Carla C. Baan

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)2420-2433
Number of pages14
JournalTransplantation
Volume108
Issue number12
DOIs
Publication statusPublished - Dec 2024

Bibliographical note

Publisher Copyright:
© 2024 The Author(s).

Fingerprint

Dive into the research topics of 'Repeated COVID-19 Vaccination Drives Memory T- and B-cell Responses in Kidney Transplant Recipients: Results From a Multicenter Randomized Controlled Trial'. Together they form a unique fingerprint.

Cite this