Lung-Resident SARS-CoV-2 Peptide-Specific Immune Responses in Perfused 3D Human Lung Explant Models

Kayla Goliwas^1*Anthony Wood¹Scott Simmons¹Saad A Khan¹Rabisa Khan¹Yong Wang¹Rekha Ramachandran¹Joel Berry¹Mohammad Athar¹James Mobley¹Young-il Kim¹Victor J. Thannickal²Kevin S Harrod¹James Donahue¹Jessy Deshane^1*

• ¹University of Alabama at Birmingham, Birmingham, United States
• ²Tulane University, New Orleans, Louisiana, United States

Multi-specific and long-lasting T cell immunity has been recognized to indicate 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 the role of lung resident memory T cells (lung TRM) in SARS-CoV-2 infection is still being investigated. This is in part due to the lack of preclinical tissue models available to follow the convalescence period. Here, we utilize a perfused three-dimensional (3D) human lung tissue model and show preexisting 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 + subjects. Importantly, we identify SARS-CoV-2 peptide-responding memory B cells and IgA + plasma cells in ex vivo cultured lung tissues of COVID-19 + . Further, lung tissue IgA levels were increased in COVID-19 + and responded to peptide stimulation. Our study highlights the importance of utilization of human lung tissue models to understand the local anti-viral immune response in the lung to protect against SARS-CoV-2 infection.