Intramuscular COVID-19 Vaccination Elicits SARS-CoV-2 Spike-Specific CD8 Tissue-Resident Memory T Cells in the Nasal Tissue

SUMMARYIn the present study, we investigated whether intramuscular COVID-19 vaccination elicits SARS-CoV-2 spike (S)-specific T cells in the nasal mucosa. During sinus surgery, nasal tissue samples were obtained from unexposed individuals, vaccinated individuals without infection, and vaccinated individuals with breakthrough infection (BTI). In all three patient groups, analysis of activation-induced markers revealed nasal S-reactive T cells that expressed tissue-resident markers, including CD69, CD103, and CXCR6. We next performed MHC-I multimer staining to examine nasal S-specific CD8+ T cells. Multimer+ CD8+ T cells with tissue-resident phenotypes were present among nasal cells from not only vaccinees with BTI but also vaccinees without infection, with no difference in frequency between these two groups. Moreover, upon ex vivo stimulation with cognate peptides, nasal multimer+ CD8+ T cells from both patient groups exerted immediate effector functions. These findings show that intramuscular COVID-19 vaccination elicits nasal S-specific CD8+ tissue-resident memory T cells that can exert immediate effector functions.Funding Information: This work was supported by the Korea Mouse Phenotyping Project (2016M3A9D5A01952414) of the Ministry of Science and ICT (MSIT) through the National Research Foundation (NRF), the NRF grants funded by the Korea government (MSIT) (No. 2016R1A5A2008630 and No.2019R1A2C1089841), and the Basic Science Research Program through the NRF funded by the Ministry of Education (2021R1I1A1A01047571).Declaration of Interests: The authors have no conflicts of interest.Ethics Approval Statement: This study was reviewed and approved by the institutional review boards 17 of Severance Hospital (no. 4-2021-0573) and Chungnam National University Hospital (2018-12-025). Informed consent was obtained from all donors, and this study was conducted according to the principles of the Declaration of Helsinki.