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

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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Journal
Blood Advances
Published
2026-04-06
DOI
https://doi.org/10.1182/bloodadvances.2026019614
Primary Topic
SARS-CoV-2 and COVID-19 Research
Type
article
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article

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

Marcie Riches, Kinga Hosszu, John M. McCarty, Kavita V. Bhavsar et al.
Blood Advances
SARS-CoV-2 and COVID-19 Research
article

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

Marcie Riches, Kinga Hosszu, John M. McCarty, Kavita V. Bhavsar, Elad Sharon, Susan DeWolf, Lik Wee Lee, Aliyah Baluch, Lee M. Greenberger, Joseph P. McGuirk, Jo‐Anne H. Young, Ashley Spahn, Kristin Peyton, Sigrun Einarsdottir, Jianqun Kou, Paul M. Armistead, Jeffery J. Auletta, Zainab Shahid, Peter Westervelt, Mary Horowitz, Teng Fei, Stephanie Lynn Waldvogel, Katina H. Singh, Joshua A. Hill, Miguel-Angel Perales, Ryotaro Nakamura, Madhav V. Dhodapkar, Mehdi Hamadani, Min Chen, Michael J. Martens, Amir Ahmed Toor
article en

Abstract

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.

Blood Advances
University of North Carolina at Chapel Hill (US), City Of Hope National Medical Center (US), National Marrow Donor Program (US), Memorial Sloan Kettering Cancer Center (US), Virginia Commonwealth University (US), Medical College of Wisconsin (US), Washington University in St. Louis (US), University of Minnesota System (US), Sahlgrenska University Hospital (SE), Moffitt Cancer Center (US), Fred Hutch Cancer Center (US), The University of Kansas Cancer Center (US), Adaptive Biotechnologies (United States) (US), City of Hope (US), Center for Cancer and Blood Disorders (US), Emmes (United States) (US), Dana-Farber Cancer Institute (US), Creative Health Care Management (US), The University of Texas Southwestern Medical Center (US)
Good health and well-being
Openalex Percentile: Top 28%
SARS-CoV-2 and COVID-19 Research
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