Local SARS-CoV-2 peptide-specific Immune Responses in Convalescent and Uninfected Human Lung Tissue Models.

Multi-specific and long-lasting T cell immunity have been recognized as indicators for long term protection against pathogens including the novel coronavirus SARS-CoV-2, the causative agent of the COVID-19 pandemic. Functional significance of peripheral memory T cell subsets in COVID-19 convalescents (CONV) are beginning to be appreciated; but little is known about lung resident memory T cell (lung TRM) responses and their role in limiting the severity of SARS-CoV-2 infection. Here, we utilize a perfusion three dimensional (3D) human lung tissue model and identify pre-existing local T cell immunity against SARS-CoV-2 spike protein and structural antigens in the lung tissues. We report ex vivo maintenance of functional multi-specific IFN-γ secreting lung TRM in CONV and their induction in lung tissues of vaccinated CONV. Importantly, we identify SARS-CoV-2 spike peptide-responding B cells in lung tissues of CONV in ex vivo 3D-tissue models. Our study highlights a balanced and local anti-viral immune response in the lung and persistent induction of TRM cells as an essential component for future protection against SARS-CoV-2 infection. Further, our data suggest that inclusion of multiple viral antigens in vaccine approaches may broaden the functional profile of memory T cells to combat the severity of coronavirus infection.