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-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-γ-, TNF-α-, and IFN-γ/TNF-α-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 monofunctional 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.