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

By Kayla F. Goliwas, Christopher S. Simmons, Saad A. Khan, Anthony M. Wood, Yong Wang, Joel L. Berry, Mohammad Athar, James A Mobley, Young-il Kim, Victor J Thannickal, Kevin S Harrod, James M Donahue, Jessy S. Deshane

Posted 06 Sep 2021
medRxiv DOI: 10.1101/2021.09.02.21263042

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-{gamma} 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.

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