Increased CD8 T‐cell immunity after COVID‐19 vaccination in lymphoid malignancy patients lacking adequate humoral response: An immune compensation mechanism?

Abstract

SARS-CoV-2 vaccine immunogenicity is commonly evaluated by measuring antibody titers against the SARS-CoV-2 Spike (S) protein. Previously, inferior humoral vaccination responses in patients with lymphoid malignancies have been shown. 1 This can be attributed to immune defects caused by disease or treatment. NHL and CLL treated with CD20-and MM with CD38-directed therapies, leads to longlasting B-or plasma-cell depletion, respectively. CLL and MM are associated with hypogammaglobulinemia and aberrations in T-cell function. T-cell immunity is vital for viral clearance and long-lasting protection against COVID-19 after vaccination. 2 Moreover, high CD8 + T-cells contribute to COVID-19 survival in hematological patients. 3 Studies investigating T-cell responses after vaccination in patients with lymphoid malignancies are, however, scarce and results are conflicting. This leaves a knowledge gap, underlining the urgency of an in-depth and reproducible analysis of functional SARS-CoV-2 specific T-cell responses following vaccination in hematological patients. Patients. Adult patients diagnosed with CLL, NHL, or MM at two tertiary care centers in the Netherlands undergoing SARS-CoV-2 vaccination were included in the study. Serological and T-cell responses

SARS-CoV-2 vaccine-induced humoral and cellular immunity in patients with hematologic malignancies

“…Patients with multiple myeloma were reported to have inferior CD4+ T cell responses to a 2-dose vaccination schedule, possibly related to the use of dexamethasone and/or anti-CD38-directed therapy ( Figure 1 C). [50] The negative association of steroids with T cell responses after vaccination was reported by others as well. [28] A 3 rd vaccination in patients with multiple myeloma on therapy led to an increase in cytokine-producing CD4 T cells, [34] which suggests that a 3-dose vaccination schedule enhances T cell immunity in these patients, as observed in healthy individuals.…”

“…More than 70% of B cell-depleted patients did generate cellular responses after SARS-CoV-2 vaccination, [45] a discordance confirmed later by others ( Figure 1 D). [ 47 , 50 , 51 ] In the absence of a humoral response, the proportions of spike-specific CD8+ T cells were significantly higher compared to proportions observed in individuals with an intact humoral response, suggesting an immune compensatory mechanism. [50] Whether vaccine-induced CD8+ T cell responses provide protection against severe infection and related mortality in these B cell-depleted patients is unclear.…”

“… [32] C. Cellular immune response after second SARS-CoV-2 vaccination in patients with hematologic malignancies, stratified by patient cohort. [ 29 , 45 , 47 , 50 , 51 ] Bars indicate the percentage of patients that obtained a cellular immune response, defined by ≥40 spot forming units per 10 6 PBMC measured by IFN-γ ELISPOT assay ≥14 days after second mRNA vaccination, [ 47 , 68 ] or 14-28 days after second ChAdOx1 or BNT162b2 vaccination, [45] or defined by the presence of SARS-CoV-2-specific IFN-γ production in the LIAISON QuantiFERON-TB Gold Plus whole blood assay ≥21 days after second mRNA-1273 vaccination, [29] or defined by the presence of ≥0.05% spike-protein reactive CD4+ T cells or ≥0.005% spike-protein reactive CD8+ T cells after stimulation with a SARS-CoV-2-spike peptide pool, ≥14 days after mRNA vaccination. [50] Orange: multiple myeloma; dark orange: lymphoid malignancies; light purple: lymphomas; dark purple: cell therapy; red: CLL.…”

“…References are indicated between brackets. [ 29 , 45 , 47 , 50 ] (No): patients not receiving immunochemotherapy; (on): patients on immunochemotherapy. When “(no)” or “(on)” is not mentioned in the Figure, literature did not determine humoral and cellular responses together in subgroups of treated or untreated patients within the hematologic malignancy.…”

“…[ 47 , 50 , 51 ] In the absence of a humoral response, the proportions of spike-specific CD8+ T cells were significantly higher compared to proportions observed in individuals with an intact humoral response, suggesting an immune compensatory mechanism. [50] Whether vaccine-induced CD8+ T cell responses provide protection against severe infection and related mortality in these B cell-depleted patients is unclear. Observations in patients with inborn errors of immunity, such as patients with agammaglobulinemia or common variable immunodeficiency, who have a dysfunctional or absent humoral immune response, suggest that other components of the immune system, including T cell immunity, are important in the prevention of severe COVID-19 and COVID-19-related death.…”