Role of SARS-CoV-2-specific memory B cells promoting immune protection after booster vaccination in solid organ transplantation.
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Donadeu Laura, Gomez-Olles Susana, Casanova Franc, Torija Alba, Lopez-Meseguer Manuel, Boada-Pérez Meritxell, Kervella Delphine, Crespo Elena, Carrera-Muñoz Claudia, Campos-Varela Isabel, Castells Lluís, Cortese Maria F, Esperalba Juliana, Fernández-Naval Candela, Quintero Jesús, Muñoz Marina, Agüero Fernando, Gonzalez-Costello José, Lladó Laura, Favà Alexandre, Cañas Laura, Del Mar de la Hoz-Caballero María, Meneghini Maria, Torres Irina B, Juvé Mariona, Hafkamp Fmj, Vila Marta, Robles Alba G, Buzón Maria José, Toapanta Nestor, Zúñiga José Miguel, Monforte Víctor, Saez-Giménez Berta, Len Oscar, Arcos Ibai Los, Miret Enric, Ariceta Gema, Pardo Emma, Martínez Xavier, Moreso Francesc, Bestard Oriol
Аннотация
METHODS: We investigated the function and interplay of SARS-CoV-2-specific memory B cells (mBc), different cytokineproducing T cells, and cross-reactive NAb in driving seroconversion and protection against COVID-19 in two cohorts. First, we studied a large cohort of 148 SOT recipients and 32 immunocompetent individuals who underwent several vaccinations. Subsequently, we assessed 25 SOT patients participating in a randomized controlled trial to compare two different immunosuppressive strategies for allowing successful seroconversion and memory-cell responses after booster vaccination.
RESULTS: We corroborate previous findings that B- and T-cell memory responses are weaker and more delayed in SOT patients than in immunocompetent (IC) individuals; however, within the SOT cohort, we found that these responses are relatively stronger and more robust in patients not receiving mycophenolate mofetil (MMF)-based therapies. Anti- spike IgG titers strongly correlated with RBD-specific IgG-producing mBc, with both displaying broad viral cross reactivity. Prebooster SARS-CoV-2-specific mBc and IL-2- producing T cells accurately predicted Nab seroconversion (AUC, 0.828) and protection against severe COVID-19. While switching unresponsive SOT patients from calcineurin inhibitors (CNI)/MMF to a low-exposure CNI/mTOR-i regimen favored wider SARS-CoV-2-specific immune responses after a fourth booster vaccination, preformed RBD-specific mBc predicted NAb seroconversion.
DISCUSSION: Our study adds new insights into the pathobiology of immune memory and highlights the pivotal role of SARS-CoV-2-specific mBc in promoting immune protection inSOT patients.