Role of SARS-CoV-2-specific memory B cells promoting immune protection after booster vaccination in solid organ transplantation
Year: 2024
Type: article
Abstract: Introduction: Solid organ transplant (SOT) recipients display weak seroconversion and neutralizing antibody (NAb) responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and remain at risk of severe coronavirus disease 2019 (COVID-19). While B-cell memory is the hallmark of serological immunity, its role in driving successful vaccine responses and providing immune protection in SOT patients remains unclear. 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.
Source: Frontiers in Immunology
Authors: Laura Donadeu, Susana Gomez-Olles, Franc Casanova, Alba Torija, Manuel Lopez-Meseguer, Meritxell Boada-Pérez, Delphine Kervella, Elena Crespo, Claudia Carrera-Muñoz, Isabel Campos-Varela, Lluís Castells, Maria F. Cortese, Juliana Esperalba, Candela Fernández-Naval, Jesús Quintero, Marina Muñoz, Fernando Agüero, José Gonzalez-Costello, Laura Lladó, Alexandre Favà, Laura Cañas, María del Mar de la Hoz-Caballero, Maria Meneghini, Irina B. Torres, Mariona Juvé, FMJ Hafkamp, Marta Vila, Alba G. Robles, Maria José Buzón, Nestor Toapanta, José Miguel Zúñiga, Víctor Monforte, Berta Saez-Giménez, Oscar Len, Ibai Los Arcos, Enric Miret, Gema Ariceta, Emma Pardo, Xavier Martínez, Francesc Moreso, Oriol Bestard
Institutions: Universitat Autònoma de Barcelona, Vall d'Hebron Institut de Recerca, Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Vall d'Hebron Hospital Universitari, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Bellvitge University Hospital, Institut d'Investigació Biomédica de Bellvitge, Universitat de Barcelona, Institut Català de la Salut
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,295
Awards: G3114265307, G434337789, The EUropean TRAnsplantation and INnovation (EU-TRAIN) consortium for improving diagnosis and risk stratification in kidney transplant patients, Evaluación de la sarcopenia en pacientes con cirrosis hepática mediante bioimpedancia y ecografía de muslo, Mecanismos y dianas terapéuticas de la respuesta Inmunológica Humoral de Memoria facilitando el rechazo del injerto en el trasplante renal, Disección y promoción de inmunidad adaptativa específica frente al poliomavirus (BKV) para prevenir la infección viral tras el trasplante renal (proyecto BK-VAX)
OpenAlex ID: W4403237746