tetano
Editor, Senior Moderator
Front Immunol
. 2024 Oct 8:15:1463769.
doi: 10.3389/fimmu.2024.1463769. eCollection 2024. Role of SARS-CoV-2-specific memory B cells promoting immune protection after booster vaccination in solid organ transplantation
Laura Donadeu[SUP] 1 2 [/SUP], Susana Gomez-Olles[SUP] 2 3 4 [/SUP], Franc Casanova[SUP] 1 2 [/SUP], Alba Torija[SUP] 1 2 [/SUP], Manuel Lopez-Meseguer[SUP] 2 3 4 5 [/SUP], Meritxell Boada-Pérez[SUP] 2 3 [/SUP], Delphine Kervella[SUP] 1 2 6 [/SUP], Elena Crespo[SUP] 1 2 [/SUP], Claudia Carrera-Muñoz[SUP] 1 2 6 [/SUP], Isabel Campos-Varela[SUP] 2 7 8 [/SUP], Lluís Castells[SUP] 2 7 [/SUP], Maria F Cortese[SUP] 9 [/SUP], Juliana Esperalba[SUP] 2 9 [/SUP], Candela Fernández-Naval[SUP] 9 [/SUP], Jesús Quintero[SUP] 2 10 [/SUP], Marina Muñoz[SUP] 2 11 [/SUP], Fernando Agüero[SUP] 12 [/SUP], José Gonzalez-Costello[SUP] 13 [/SUP], Laura Lladó[SUP] 14 [/SUP], Alexandre Favà[SUP] 15 [/SUP], Laura Cañas[SUP] 16 [/SUP], María Del Mar de la Hoz-Caballero[SUP] 17 [/SUP], Maria Meneghini[SUP] 1 2 6 [/SUP], Irina B Torres[SUP] 2 6 [/SUP], Mariona Juvé[SUP] 1 [/SUP], Fmj Hafkamp[SUP] 1 2 [/SUP], Marta Vila[SUP] 9 [/SUP], Alba G Robles[SUP] 18 [/SUP], Maria José Buzón[SUP] 18 [/SUP], Nestor Toapanta[SUP] 2 6 [/SUP], José Miguel Zúñiga[SUP] 1 2 6 [/SUP], Víctor Monforte[SUP] 2 3 5 [/SUP], Berta Saez-Giménez[SUP] 2 3 5 [/SUP], Oscar Len[SUP] 2 19 [/SUP], Ibai Los Arcos[SUP] 2 19 [/SUP], Enric Miret[SUP] 2 20 [/SUP], Gema Ariceta[SUP] 2 11 [/SUP], Emma Pardo[SUP] 6 [/SUP], Xavier Martínez[SUP] 21 [/SUP], Francesc Moreso[SUP] 2 6 [/SUP], Oriol Bestard[SUP] 1 2 6 [/SUP]
Affiliations
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.
Keywords: SARS-CoV-2; adaptive immunity; booster vaccination; neutralizing antibodies; solid organ transplantation.
. 2024 Oct 8:15:1463769.
doi: 10.3389/fimmu.2024.1463769. eCollection 2024. Role of SARS-CoV-2-specific memory B cells promoting immune protection after booster vaccination in solid organ transplantation
Laura Donadeu[SUP] 1 2 [/SUP], Susana Gomez-Olles[SUP] 2 3 4 [/SUP], Franc Casanova[SUP] 1 2 [/SUP], Alba Torija[SUP] 1 2 [/SUP], Manuel Lopez-Meseguer[SUP] 2 3 4 5 [/SUP], Meritxell Boada-Pérez[SUP] 2 3 [/SUP], Delphine Kervella[SUP] 1 2 6 [/SUP], Elena Crespo[SUP] 1 2 [/SUP], Claudia Carrera-Muñoz[SUP] 1 2 6 [/SUP], Isabel Campos-Varela[SUP] 2 7 8 [/SUP], Lluís Castells[SUP] 2 7 [/SUP], Maria F Cortese[SUP] 9 [/SUP], Juliana Esperalba[SUP] 2 9 [/SUP], Candela Fernández-Naval[SUP] 9 [/SUP], Jesús Quintero[SUP] 2 10 [/SUP], Marina Muñoz[SUP] 2 11 [/SUP], Fernando Agüero[SUP] 12 [/SUP], José Gonzalez-Costello[SUP] 13 [/SUP], Laura Lladó[SUP] 14 [/SUP], Alexandre Favà[SUP] 15 [/SUP], Laura Cañas[SUP] 16 [/SUP], María Del Mar de la Hoz-Caballero[SUP] 17 [/SUP], Maria Meneghini[SUP] 1 2 6 [/SUP], Irina B Torres[SUP] 2 6 [/SUP], Mariona Juvé[SUP] 1 [/SUP], Fmj Hafkamp[SUP] 1 2 [/SUP], Marta Vila[SUP] 9 [/SUP], Alba G Robles[SUP] 18 [/SUP], Maria José Buzón[SUP] 18 [/SUP], Nestor Toapanta[SUP] 2 6 [/SUP], José Miguel Zúñiga[SUP] 1 2 6 [/SUP], Víctor Monforte[SUP] 2 3 5 [/SUP], Berta Saez-Giménez[SUP] 2 3 5 [/SUP], Oscar Len[SUP] 2 19 [/SUP], Ibai Los Arcos[SUP] 2 19 [/SUP], Enric Miret[SUP] 2 20 [/SUP], Gema Ariceta[SUP] 2 11 [/SUP], Emma Pardo[SUP] 6 [/SUP], Xavier Martínez[SUP] 21 [/SUP], Francesc Moreso[SUP] 2 6 [/SUP], Oriol Bestard[SUP] 1 2 6 [/SUP]
Affiliations
- PMID: 39439787
- PMCID: PMC11493670
- DOI: 10.3389/fimmu.2024.1463769
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.
Keywords: SARS-CoV-2; adaptive immunity; booster vaccination; neutralizing antibodies; solid organ transplantation.