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Local SARS-CoV-2 peptide-specific Immune Responses in Lungs of Convalescent and Uninfected Human Subjects

By Kayla F. Goliwas, Anthony M. Wood, Christopher S. Simmons, Rabisa J. Khan, Saad A. Khan, 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 cells in individuals recovering from COVID-19 (COVID-19+) are beginning to be appreciated; but little is known about lung resident memory T cells (lung TRM) in SARS-CoV-2 infection. Here, we utilize a perfused three dimensional (3D) human lung tissue model and identify pre-existing local T cell immunity against SARS-CoV-2 proteins in lung tissues. We report ex vivo maintenance of functional multi-specific IFN-{gamma} secreting lung TRM in COVID-19+ and their induction in lung tissues of vaccinated COVID-19+. Importantly, we identify SARS-CoV-2 peptide-responding B cells and IgA+ plasma cells in lung tissues of COVID-19+ in ex vivo 3D-tissue models. Our study highlights the importance of balanced and local anti-viral immune response in the lung with persistent induction of TRM and IgA+ plasma cells 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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