Robust SARS-CoV-2 T cell responses with common TCRαβ motifs toward COVID-19 vaccines in patients with hematological malignancy impacting B cells

Immunocompromised hematology patients are vulnerable to severe COVID-19 and respond poorly to vaccination. Relative deficits in immunity are, however, unclear, especially after 3 vaccine doses. We evaluated immune responses in hematology patients across three COVID-19 vaccination doses. Seropositivity was low after a first dose of BNT162b2 and ChAdOx1 (∼26%), increased to 59%–75% after a second dose, and increased to 85% after a third dose. While prototypical antibody-secreting cells (ASCs) and T follicular helper (Tfh) cell responses were elicited in healthy participants, hematology patients showed prolonged ASCs and skewed Tfh2/17 responses. Importantly, vaccine-induced expansions of spike-specific and peptide-HLA tetramer-specific CD4+/CD8+ T cells, together with their T cell receptor (TCR) repertoires, were robust in hematology patients, irrespective of B cell numbers, and comparable to healthy participants. Vaccinated patients with breakthrough infections developed higher antibody responses, while T cell responses were comparable to healthy groups. COVID-19 vaccination induces robust T cell immunity in hematology patients of varying diseases and treatments irrespective of B cell numbers and antibody response. [Display omitted] •COVID-19 vaccines elicit robust SARS-CoV-2-specific T cells in hematology patients•Prevalent TCRαβ motifs occur within tetramer+ T cells in hematological patients•Conversely, perturbed antibody responses and skewing of Tfh and ASC/Tfh kinetics occur•Breakthrough infection patients have higher antibodies and comparable T cell responses Nguyen et al. define antibody, B, and T cell responses following COVID-19 vaccination in patients with hematological malignancy that are immunocompromised and vulnerable to severe COVID-19 infection. COVID-19 vaccination induces robust T cell immunity in hematology patients with diseases and treatments impacting B cell immunity irrespective of B cell numbers and antibody responses.