Antigen-specific T cell responses to SARS-CoV-2 vaccination after Hematopoietic Cell Transplant or CAR T cell Therapy

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The optimal timing of SARS-CoV-2 vaccination after cellular therapies remains uncertain. In a prior prospective multicenter cohort (n=466), we found no differences in humoral or SARS-CoV-2-specific T cell receptor (TCR) responses between patients vaccinated early (<4 months) versus later (4-12 months) after allogeneic hematopoietic cell transplant (allo-HCT), autologous HCT (auto-HCT), or chimeric antigen receptor T cell (CAR-T) therapy. In this sub-study, we evaluated functional T cell responses in 68 patients (allo-HCT n=28, auto-HCT n=22, CAR-T n=18) that were clinically and immunophenotypically similar to the overall cohort. Antigen-specific CD4⁺ and CD8⁺ T cell responses to SARS-CoV-2 mRNA vaccination were assessed by spectral flow cytometry. Functional responses were correlated with baseline immune reconstitution parameters, antibody responses, and to SARS-CoV-2-specific TCR repertoire metrics. Vaccination induced significant increases in antigen-specific IFN-γ and TNF-α production by both CD4⁺ and CD8⁺ T cells across all cellular therapy groups. Responses were primarily driven by CD4⁺ central memory and cytotoxic CD8⁺ T cell subsets. Functional T cell responses correlated with baseline CD19⁺ B cell counts (p=0.002) and post-vaccination antibody responses (p<0.01), but not with SARS-CoV-2-specific TCR breadth or depth. Notably, functional T cell responses were detectable even in patients with low B cell counts or absent antibody responses. We conclude that mRNA SARS-CoV-2 vaccination elicits functional, Th1-skewed T cell responses after allo-HCT, auto-HCT, and CAR-T therapy. Initiation of SARS-CoV-2 vaccination early after cellular therapy (<4 months) was not associated with impaired functional T cell responses.

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