Maintenance and functional regulation of immune memory to COVID-19 vaccines in tissues
Memory T and B cells in lymphoid and mucosal tissues maintain long-term protection, though their generation following vaccination remains challenging to assess in humans. Here, we investigated immune memory generated to COVID-19 mRNA vaccines across blood, lymphoid organs, and lungs from 42 vaccinated organ donors aged 23-86, of whom 57% were previously infected with SARS-CoV-2. This was facilitated using FACS with the activation-induced marker (AIM) assay for T lymphocytes to peptide mega pools (SARS-COV2 and Influenza) and using spike protein conjugated fluorophores to identify spike (S) specific B cells. Using high-dimensional profiling, we reveal that Spike (S)-reactive memory T cells distribute in lymphoid organs and lungs, variably express tissue resident markers based on infection history, and exhibit site-specific compositions of effector and regulatory memory T cells. S-reactive B cells are mostly class-switched memory cells localized to lymphoid organs correlating with circulating antibodies. Importantly, tissue memory T cells are more stably maintained post-vaccination and over age and exhibit a bias towards regulatory cell functional profiles compared to circulating populations. Our results show that mRNA vaccines can induce heterogeneous memory populations across sites for protection and controlling immune pathology. Overall design: We performed CITE-seq on AIM+ and AIM- immune cell populations in response to SARS-COV-2 (or influenza) peptide megapools from human blood and different human organ donor tissues.