Gao Y, Cai C, Wullimann D, Niessl J, Rivera-Ballesteros O, Chen P, Lange J, Cuapio A, Blennow O, Hansson L, Mielke S, Nowak P, Vesterbacka J, Akber M, Perez-Potti A, Sekine T, Müller TR, Boulouis C, Kammann T, Parrot T, Muvva JR, Sobkowiak M, Healy K, Bogdanovic G, Muschiol S, Söderdahl G, Österborg A, Hellgren F, Grifoni A, Weiskopf D, Sette A, Loré K, Sällberg Chen M, Ljungman P, Sandberg JK, Smith CIE, Bergman P, Ljunggren HG, Aleman S, Buggert M
Immunity 55 (9) 1732-1746.e5 [2022-09-13; online 2022-07-19]
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.