Robust SARS-CoV-2 T cell responses with common TCRab 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 vacci-nation. 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 pep-tide-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. Vacci-nated 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.

Automated summary

Immunocompromised hematology patients respond poorly to COVID-19 vaccination, but robust T cell immunity is induced, regardless of B cell numbers and antibody response. Seropositivity rates increase with each vaccine dose. Hematology patients show prolonged ASCs and skewed Tfh2/17 responses, but their T cell responses are comparable to healthy individuals. Breakthrough infections in vaccinated patients result in higher antibody responses but similar T cell responses to healthy groups.