Airway surveillance and lung viral control by memory T cells induced by COVID-19 mRNA vaccine

Although SARS-CoV-2 evolution seeds a continuous stream of antibody-evasive viral variants, COVID-19 mRNA vaccines provide robust protection against severe disease and hospitalization. Here, we asked whether mRNA vaccine-induced memory T cells limit lung SARS-CoV-2 replication and severe disease. We...

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Bibliographic Details
Published in:JCI insight 2023-11, Vol.8 (22)
Main Authors: Kingstad-Bakke, Brock, Cleven, Thomas, Bussan, Hailey, Yount, Jr, Boyd L, Uraki, Ryuta, Iwatsuki-Horimoto, Kiyoko, Koga, Michiko, Yamamoto, Shinya, Yotsuyanagi, Hiroshi, Park, Hongtae, Mishra, Jay S, Kumar, Sathish, Baric, Ralph S, Halfmann, Peter J, Kawaoka, Yoshihiro, Suresh, M
Format: Article
Language:English
Subjects:
Animals
COVID-19
COVID-19 - prevention & control
COVID-19 Vaccines
Humans
Immunology
Lung
Memory T Cells
Mice
SARS-CoV-2
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Summary:Although SARS-CoV-2 evolution seeds a continuous stream of antibody-evasive viral variants, COVID-19 mRNA vaccines provide robust protection against severe disease and hospitalization. Here, we asked whether mRNA vaccine-induced memory T cells limit lung SARS-CoV-2 replication and severe disease. We show that mice and humans receiving booster BioNTech mRNA vaccine developed potent CD8 T cell responses and showed similar kinetics of expansion and contraction of granzyme B/perforin-expressing effector CD8 T cells. Both monovalent and bivalent mRNA vaccines elicited strong expansion of a heterogeneous pool of terminal effectors and memory precursor effector CD8 T cells in spleen, inguinal and mediastinal lymph nodes, pulmonary vasculature, and most surprisingly in the airways, suggestive of systemic and regional surveillance. Furthermore, we document that: (a) CD8 T cell memory persists in multiple tissues for > 200 days; (b) following challenge with pathogenic SARS-CoV-2, circulating memory CD8 T cells rapidly extravasate to the lungs and promote expeditious viral clearance, by mechanisms that require CD4 T cell help; and (c) adoptively transferred splenic memory CD8 T cells traffic to the airways and promote lung SARS-CoV-2 clearance. These findings provide insights into the critical role of memory T cells in preventing severe lung disease following breakthrough infections with antibody-evasive SARS-CoV-2 variants.
ISSN:2379-3708
2379-3708
DOI:10.1172/jci.insight.172510