期刊
IMMUNITY
卷 55, 期 9, 页码 1732-+出版社
CELL PRESS
DOI: 10.1016/j.immuni.2022.07.005
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资金
- SciLifeLab National COVID-19 Research Program
- Knut and Alice Wallenberg Foundation
- Swedish Research Council
- Region Stockholm
- Nordstjernan AB
- Karolinska Institutet
- Swedish patient organizations of Primary Immunodeficiencies (PIO) and Hematology (Swedish Blood Cancer Foundation)
- Karolinska Institutet
- European Research Council
- Swedish Society of Medicine
- Ake Wibergs Stiftelse
- Swedish Cancer Society
- Jonas Soderquist Stiftelse
- Swedish Childhood Cancer Fund
- NIH [75N9301900065]
- EMBO postdoctoral fellowship [ALTF 1062-2020]
- National Genomics Infrastructure in Stockholm - Science for Life Laboratory
Many immunocompromised patients have suboptimal cell-mediated immunity after SARS-CoV-2 mRNA vaccination, particularly solid-organ transplant and chronic lymphocytic leukemia patients. However, individuals with X-linked agammaglobulinemia (XLA) showed highly functional spike-specific T cell responses. The study also revealed a broad functional spectrum of spike-specific CD4(+) and CD8(+) T cells in healthy individuals and XLA patients after mRNA vaccination.
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.
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