Immunodeficiency syndromes differentially impact the functional profile of SARS-CoV-2-specific T cells elicited by mRNA vaccination

Immunity. 2022 Sep 13;55(9):1732-1746.e5. doi: 10.1016/j.immuni.2022.07.005. Epub 2022 Jul 19.


Many immunocompromised patients mount suboptimal humoral immunity after SARS-CoV-2 mRNA vaccination. Here, we assessed the single-cell profile of SARS-CoV-2-specific T cells post-mRNA vaccination in healthy individuals and patients with various forms of immunodeficiencies. Impaired vaccine-induced cell-mediated immunity was observed in many immunocompromised patients, particularly in solid-organ transplant and chronic lymphocytic leukemia patients. Notably, individuals with an inherited lack of mature B cells, i.e., X-linked agammaglobulinemia (XLA) displayed highly functional spike-specific T cell responses. Single-cell RNA-sequencing further revealed that mRNA vaccination induced a broad functional spectrum of spike-specific CD4+ and CD8+ T cells in healthy individuals and patients with XLA. These responses were founded on polyclonal repertoires of CD4+ T cells and robust expansions of oligoclonal effector-memory CD45RA+ CD8+ T cells with stem-like characteristics. Collectively, our data provide the functional continuum of SARS-CoV-2-specific T cell responses post-mRNA vaccination, highlighting that cell-mediated immunity is of variable functional quality across immunodeficiency syndromes.

Keywords: COVID-19; SARS-CoV-2; T cells; mRNA vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral
  • CD8-Positive T-Lymphocytes
  • COVID-19* / prevention & control
  • Humans
  • Immunity, Humoral
  • RNA, Messenger / genetics
  • SARS-CoV-2*
  • Syndrome
  • Vaccination
  • Viral Envelope Proteins


  • Antibodies, Viral
  • RNA, Messenger
  • Viral Envelope Proteins