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

Abstract

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.

Innate and Adaptive Immune Parameters following mRNA Vaccination in Mice

“…First, all mRNA vaccinations (mRNA-S, N, and S+N) led to a gene expression profile predominantly related to host immunity in the lung, which is less evident in the spleen at 2 weeks post booster immunization. These data indicate the induction of airway immune response and are consistent with prior reports on the mRNA vaccine-induced expansion of T cells in multiple tissues, including mouse and human airway tissues [33]. Second, the transcriptomic signature includes the upregulation of a range of DEGs involved in T-cell function, cytokine signaling, and antigen presentation, which is consistent with our earlier report showing the induction of strong CD4 + and CD8 + T-cell responses by both mRNA-N and mRNA-S [5].…”