SARS-CoV-2 spike-directed T cells and anti-receptor-binding-domain antibodies in hematological patients receiving three mRNA COVID-19 vaccine doses

Introduction: Studies assessing SARS-CoV-2 antibodies and functional T-cell responses in hematological patients following receipt of a three-dose mRNA vaccine schedule have yielded conflicting results. Methods: We conducted a retrospective observational study in which we measured SARS-CoV-2-S-direct...

Descripción completa

Detalles Bibliográficos
Autores: Carretero, D, Giménez, E, Pérez, A, Hernani, R, Piñana, JL, Solano, C, Navarro, D, Albert, E
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2026
País:España
Institución:INCLIVA
Repositorio:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:dnet:incliva_____::004e046d2cc42f242f6ef274c7d8b05e
Acceso en línea:https://incliva.portalinvestigacion.com/publicaciones/20799
Access Level:acceso abierto
Palabra clave:SARS-CoV-2
COVID-19 vaccine
T-cell immunity
Anti-RBD antibodies
Booster
Descripción
Sumario:Introduction: Studies assessing SARS-CoV-2 antibodies and functional T-cell responses in hematological patients following receipt of a three-dose mRNA vaccine schedule have yielded conflicting results. Methods: We conducted a retrospective observational study in which we measured SARS-CoV-2-S-directed cytokine-producing CD8+ and CD4+ T cells by flow cytometry and anti-receptor-binding domain (RBD) total antibodies in 32 hematological patients, including 10 allogeneic hematopoietic stem cell transplant (allo-HCT) recipients and 22 non-transplanted individuals. Immunological testing was performed after the second COVID-19 mRNA vaccine dose (Post-2D), prior to the third dose (Pre-3D), and after the third dose (Post-3D). Results: At Post-2D, 72.4%, 44.8%, and 37.9% of participants had detectable IFN-gamma-, TNF-alpha-, and IFN-gamma/TNF-alpha producing CD8+T cells, respectively. A decrease in the rate of detectable and frequencies of monofunctional and bifunctional SARS-CoV-2-S CD8+ T-cell responses was observed at Pre-3D. By contrast, the number of participants displaying detectable cytokine-producing CD4+ T-cell responses and their frequencies were rather conserved at all testing times. Receiving a 3D had no significant impact on the rate of detection and frequencies of monofun ctional and bifunctional SARS-CoV-2-S-directed T-cell subsets. Anti-RBD total antibody responses were detected in approximately half of participants at all time points. Overall, anti-RBD antibody levels decreased at Pre-3D and then increased following the 3D. Conclusion: Administration of the 3D may have a limited impact on both cellular and humoral immune responses in a substantial proportion of hematological patients. These findings highlight the heterogeneity of vaccine-induced immunity and support the role of combined immune monitoring and alternative protective strategies for selected patients.