Enhanced BNT162b2 vaccine-induced cellular immunity in anti-CD19 CAR T cell-treated patients

Abstract

Patients receiving CD19 CAR T-cell therapy for relapsed/refractory lymphoma experience prolonged and profound B-cell aplasia and hypogammaglobulinemia, placing them at a higher risk for severe COVID-19. Independently, Oh et al and Atanackovic et al demonstrate that despite attenuated humoral response to mRNA-based vaccines, patients demonstrate normal or heightened functional T-cell responses, including antiviral T-cell activity against SARS-CoV-2 variants including Omicron. Collectively, these data reinforce the importance of COVID-19 vaccination following CD19 CAR T-cell therapy, despite long-term B-cell aplasia.

Figure 1.

Enhanced vaccine-induced Spike-specific T-cell response in anti-CD19 CAR T cell–treated patients. Healthy individuals (n = 26) and (A) anti-CD19 CAR T cell–treated patients (n = 8) were vaccinated on days 0 and 21 with BNT162b2 mRNA vaccine. Blood samples were taken on days 0, 11, 21, 31, 42, and 90. (B) Levels of neutralizing antibodies. IFN-γ (C) and IL-2 (D) secreted into the plasma after whole blood stimulation with Spike-peptide pool and dimethyl sulfoxide control were quantified. (E) Representative flow cytometry plots for quantifying AIM+CD4 T cells. The numbers represent the percentage of total nonnaïve CD4 T cells that are AIM+ on days 0 and 42. Below, summary data of AIM+CD4 T-cell frequency before and after vaccination. The values represent the background-subtracted frequency of AIM+ nonnaïve CD4 T cells. (F) Representative flow cytometry plots for quantifying AIM+CD8 T cells. The numbers represent the percentage of total nonnaïve CD8 T cells that are AIM+ on days 0 and 42. Below, summary data of AIM+CD8 T-cell frequency before and after vaccination. The values represent the background-subtracted frequency of AIM+ nonnaïve CD8 T cells.

Figure 2.

Vaccine-induced Spike-specific T cells are multispecific and preserved against VOCs. (A) PBMCs collected on days 0 and 42 were stimulated with 7 different peptide pools covering distinct regions of the Spike protein and activation was analyzed by IFN-γ-ELISpot assay. Representative ELISpot assay is shown for 1 patient on days 0 and 42. Heatmaps indicate the percentage of the response toward a single peptide pool in proportion to the total Spike-specific response in each of the tested individuals: healthy (red) and CD19 CAR T-cell patients (blue). (B) Bar graphs show the percentage of donors (healthy, n = 7; CD19 CAR T cell, n = 8) reacting to the number of Spike peptide pools tested (total 7 distinct peptide pools). (C) Mean proportion of the response to the 7 distinct Spike peptide pools in healthy (i) and CD19 CAR-T patients (ii). (D) IFN-γ-spot forming cells (SFC) per 1 million PBMC reactive to Spike-peptide pools of the ancestral (red), Delta (blue), and Omicron (green) SARS-CoV-2 variants are shown. (E) Percentage of Spike-specific T cells reactive to the Delta (i) and Omicron (ii) SARS-CoV-2 variants is shown for all 8 patients. The pie charts indicate the mean inhibition.