Cellular and humoral immunogenicity of the mRNA-1273 SARS-CoV-2 vaccine in patients with hematologic malignancies

Abstract

Recent studies have shown a suboptimal humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in patients diagnosed with hematologic malignancies; however, data about cellular immunogenicity are scarce. The aim of this study was to evaluate both the humoral and cellular immunogenicity 1 month after the second dose of the mRNA-1273 vaccine. Antibody titers were measured by using the Elecsys and LIAISON anti-SARS-CoV-2 S assays, and T-cell response was assessed by using interferon-γ release immunoassay technology. Overall, 76.3% (184 of 241) of patients developed humoral immunity, and the cellular response rate was 79% (184 of 233). Hypogammaglobulinemia, lymphopenia, active hematologic treatment, and anti-CD20 therapy during the previous 6 months were associated with an inferior humoral response. Conversely, age >65 years, active disease, lymphopenia, and immunosuppressive treatment of graft-versus-host disease (GVHD) were associated with an impaired cellular response. A significant dissociation between the humoral and cellular responses was observed in patients treated with anti-CD20 therapy (the humoral response was 17.5%, whereas the cellular response was 71.1%). In these patients, B-cell aplasia was confirmed while T-cell counts were preserved. In contrast, humoral response was observed in 77.3% of patients undergoing immunosuppressive treatment of GVHD, whereas only 52.4% had a cellular response. The cellular and humoral responses to the SARS-CoV-2 mRNA-1273 vaccine in patients with hematologic malignancies are highly influenced by the presence of treatments such as anti-CD20 therapy and immunosuppressive agents. This observation has implications for the further management of these patients.

Graphical abstract

Figure 1.

Univariate analysis for humoral immunization rate in patients diagnosed with hematologic malignancies. Analysis of the baseline characteristics that could confer a risk to a reduced humoral immunization rate to the mRNA-1273 vaccine according to overall response rate in patients with basal negative serology immunization and no previously known SARS-CoV-2 infection. CI, confidence interval; CR, complete response; PR, partial response; SD/PD, stable disease/progressive disease.

Figure 2.

Univariate analysis for cellular immunization rate in patients diagnosed with hematologic malignancies. Analysis of the baseline characteristics that could confer a risk to a reduced cellular immunization rate to the mRNA-1273 vaccine according to overall response rate in patients with basal negative serology and T-cell immunization and no previously known SARS-CoV-2 infection. CI, confidence interval; CR, complete response; PR, partial response; SD/PD, stable disease/progressive disease.

Figure 3.

Proportion of concordance of humoral and cellular immune response to the mRNA-1273 vaccine according to baseline characteristics in patients diagnosed with hematologic malignancies. CR, complete response; PR, partial response; SD/PD, stable disease/progressive disease.

Figure 4.

Humoral and cellular immune response rate according to lymphocyte subpopulations and administered therapy. (A) In patients undergoing treatment with anti-CD20 therapy (n = 40), the influence of this monoclonal antibody's association with chemotherapy in the lymphocyte subpopulations and in the humoral or cellular response to the vaccine was determined. Abnormal values were considered as follows: CD19, >0.10 × 10⁹/L; CD3, >0.7 × 10⁹/L; CD4, 0.3 × 10⁹/L; CD8, 0.2 × 10⁹/L; and lymphopenia, 1.0 × 10⁹/L. (B) In allo-SCT patients (n = 59), the influence of treatment with immunosuppressive agents or target therapy in the lymphocyte subpopulations and in the humoral or cellular response to the vaccine was determined.