Additive effects of booster mRNA vaccination and SARS-CoV-2 Omicron infection on T cell immunity across immunocompromised states.
Thomas R MüllerTakuya SekineDarya TrubachJulia NiesslPuran ChenPeter BergmanOla BlennowLotta HanssonStephan MielkePiotr NowakJan VesterbackaMira AkberAnna OlofssonSusana Patricia Amaya HernandezYu GaoCurtis CaiGunnar SöderdahlCarl Inge Edvard SmithAnders ÖsterborgKarin LoréMargaret Sällberg ChenQamar-Un-Nisa ChaudhryHans-Gustaf LjunggrenAnnika C KarlssonSunil Kumar SainiSoo AlemanMarcus BuggertPublished in: Science translational medicine (2023)
Suboptimal immunity to SARS-CoV-2 mRNA vaccination has frequently been observed in individuals with various immunodeficiencies. Given the increased antibody evasion properties of emerging SARS-CoV-2 subvariants, it is necessary to assess whether other components of adaptive immunity generate resilient and protective responses against infection. We assessed T cell responses in 279 individuals, covering five different immunodeficiencies and healthy controls, before and after booster mRNA vaccination, as well as after Omicron infection in a subset of patients. We observed robust and persistent Omicron-reactive T cell responses that increased markedly upon booster vaccination and correlated directly with antibody titers across all patient groups. Poor vaccination responsiveness in immunocompromised or elderly individuals was effectively counteracted by the administration of additional vaccine doses. Functionally, Omicron-reactive T cell responses exhibited a pronounced cytotoxic profile and signs of longevity, characterized by CD45RA + effector memory subpopulations with stem cell-like properties and increased proliferative capacity. Regardless of underlying immunodeficiency, booster-vaccinated and Omicron-infected individuals appeared protected against severe disease and exhibited enhanced and diversified T cell responses against conserved and Omicron-specific epitopes. Our findings indicate that T cells retain the ability to generate highly functional responses against newly emerging variants, even after repeated antigen exposure and a robust immunological imprint from ancestral SARS-CoV-2 mRNA vaccination.
Keyphrases
- sars cov
- stem cells
- respiratory syndrome coronavirus
- end stage renal disease
- chronic kidney disease
- binding protein
- newly diagnosed
- ejection fraction
- rheumatoid arthritis
- early onset
- intensive care unit
- systemic lupus erythematosus
- regulatory t cells
- gene expression
- immune response
- peritoneal dialysis
- dna methylation
- drug induced
- cell therapy
- respiratory failure