Repeated COVID-19 vaccination drives memory T and B cell responses in kidney transplant recipients: Results from a multicenter randomized controlled trial
Reshwan Malahé1, Yvette den Hartog1, Wim J.R. Rietdijk2, Ronella de Kuiper1, Derek Reijerkerk1, Alicia M. Ras1, Marcia M.L. Kho1, Rory D. de Vries3, Marlies E.J. Reinders1, Carla C. Baan1.
1Department of Internal Medicine, Nephrology and Transplantation, Erasmus MC Transplant Institute, Erasmus University Medical Center, Rotterdam, Netherlands; 2Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, Netherlands; 3Department of Viroscience, Erasmus University Medical Center, Rotterdam, Netherlands
RECOVAC Consortium.
Introduction: Insight into cellular immune responses to COVID-19 vaccinations is crucial for optimizing booster programs in kidney transplant recipients (KTR).
Method: In an immunological sub-study of a multicenter randomized controlled trial (NCT05030974) investigating different repeated vaccination strategies in KTR who showed poor serological responses after two or three doses of an mRNA-based vaccine, we compared SARS-CoV-2-specific IL-21 memory T cell and B cell responses by 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 (2x 100 μg, n=25), or a single dose of 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 (MMF) or mycophenolic acid (MPA) for 2 weeks.
Results: Repeated vaccination increased memory IL-21 T cell, B cell and antibody responses in all groups, with no significant differences between various strategies. Seroconversion after repeated vaccination was strongly associated with memory T (OR 3.84 [1.89-7.78], p<0.001) and B cells (OR 35.93 [6.94-186.04], p<0.001) with the number of antigen-specific memory B cells showing potential for classifying seroconversion (AUC=0.95, CI= 0.87 to 0.97, p<0.0001).
Conclusion: Our study emphasizes the importance of virus-specific memory T and B cell responses for comprehensive understanding of COVID-19 vaccine efficacy among KTR.
Debbie van Baarle. 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 Sanders. Corine H. GeurtsvanKessel. RECOVAC collaborators.
[1] COVID-19
[2] vaccination
[3] T cells
[4] B cells
[5] cellular immune responses
[6] kidney transplant recipients
