Additive effects of booster mRNA vaccination and SARSCoV-2 Omicron infection on T cell immunity across immunocompromised states

Thomas R. Müller*, Takuya Sekine, Darya Trubach, Julia Niessl, Puran Chen, Peter Bergman, Ola Blennow, Lotta Hansson, Stephan Mielke, Piotr Nowak, Jan Vesterbacka, Mira Akber, Anna Olofsson, Susana Patricia Amaya Hernandez, Yu Gao, Curtis Cai, Gunnar Söderdahl, C. I.Edvard Smith, Anders Österborg, Karin LoréMargaret Sällberg Chen, Per Ljungman, Hans Gustaf Ljunggren, Annika C. Karlsson, Sunil Kumar Saini, Soo Aleman, Marcus Buggert*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review


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.

Original languageEnglish
Article numbereadg9452
JournalScience Translational Medicine
Issue number704
Number of pages15
Publication statusPublished - 2023


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