Faculty Collaboration Database

Antigen-specific T-cell responses to SARS-CoV-2 vaccination after hematopoietic cell transplant or CAR T-cell therapy. Blood Adv 2026 Jun 09;10(11):3945-3959

Date

04/06/2026

Pubmed ID

41941698

Pubmed Central ID

PMC13235446

DOI

10.1182/bloodadvances.2026019614

Scopus ID

2-s2.0-105040358681 (requires institutional sign-in at Scopus site)

Abstract

The optimal timing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination after cellular therapies remains uncertain. In a previous 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) vs 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 substudy, 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 that of the overall cohort. Antigen-specific CD4+ and CD8+ T-cell responses to SARS-CoV-2 messenger RNA (mRNA) vaccination were assessed by spectral flow cytometry. Functional responses were correlated with baseline immune reconstitution parameters, antibody responses, and SARS-CoV-2-specific TCR repertoire metrics. Vaccination induced significant increases in antigen-specific interferon gamma and tumor necrosis factor 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 = .002) and postvaccination antibody responses (P< .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, T helper 1-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.

Author List

Einarsdottir S, Fei T, Singh K, Martens M, Young JH, Bhavsar K, Kou J, Chen M, Lee LW, Baluch A, Dhodapkar MV, Nakamura R, Peyton K, Shahid Z, Armistead P, Westervelt P, McCarty J, McGuirk J, Hamadani M, Sharon E, Spahn A, Toor AA, Waldvogel S, Greenberger LM, Auletta JJ, Horowitz MM, Riches ML, Hosszu K, Hill JA, DeWolf S, Perales MA

Authors

Mehdi Hamadani MBBS Professor in the Medicine department at Medical College of Wisconsin
Mary M. Horowitz MS, MD Adjunct Professor in the Medicine department at Medical College of Wisconsin
Michael Martens PhD Associate Professor in the Data Science Institute department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Female
Hematopoietic Stem Cell Transplantation
Humans
Immunotherapy, Adoptive
Male
Middle Aged
T-Lymphocytes
Vaccination