AUTHOR=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 

TITLE=Role of SARS-CoV-2-specific memory B cells promoting immune protection after booster vaccination in solid organ transplantation

JOURNAL=Frontiers in Immunology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1463769

DOI=10.3389/fimmu.2024.1463769

ISSN=1664-3224

ABSTRACT=Solid organ transplant (SOT) recipients display weak seroconversion and neutralizing antibodies (NAb) responses after SARS-CoV-2 vaccination and remain at risk of severe COVID-19. B-cell memory is the hallmark of serological immunity, but their role driving successful vaccine responses and immune protection in SOT is unclear.We investigated the function and interplay of SARS-CoV-2-specific memory B cells (mBc), different cytokine-producing T-cells and cross-reactive NAb, driving seroconversion and protection against COVID-19 in two cohorts. First, in a large cohort of 148 SOT and 32 immunocompetent individuals undergoing several vaccinations and afterwards, in 25 SOT participating in a randomized controlled trial in which we assessed two different immunosuppressive strategies to allow successful seroconversion and memory-cell responses after booster vaccination.We corroborate previous findings that B and T-cell memory responses are weaker and more delayed in SOT patients than immunocompetent (IC) individuals; however, within the SOT cohort, we find 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, both displaying broad viral cross-reactivity. Pre-booster SARS-CoV-2-specific mBc and IL2producing T cells accurately predicted NAb seroconversion (AUC 0.828) and protection against severe COVID-19. While switching unresponsive SOT from CNI/MMF to low-exposure CNI/mTOR-i favored wider SARS-CoV-2-specific immune responses after a 4 th booster vaccination, preformed RBD-specific mBc predicted NAb seroconversion.Our study adds new insight on the pathobiology of immune memory and highlights the pivotal role of SARS-CoV-2-specific mBc promoting immune protection in SOT patients.