%0 Journal Article %T Salivary IgA and vimentin differentiate in vitro SARS-CoV-2 infection: A study of 290 convalescent COVID-19 patients. %A Ellis S %A Way R %A Nel M %A Burleigh A %A Doykov I %A Kembou-Ringert J %A Woodall M %A Masonou T %A Case KM %A Ortez AT %A McHugh TD %A Casal A %A McCoy LE %A Murdan S %A Hynds RE %A Gilmour KC %A Grandjean L %A Cortina-Borja M %A Heywood WE %A Mills K %A Smith CM %J Mucosal Immunol %V 17 %N 1 %D 2024 Feb 24 %M 38007005 %F 8.701 %R 10.1016/j.mucimm.2023.11.007 %X SARS-CoV-2 initially infects cells in the nasopharynx and oral cavity. The immune system at these mucosal sites plays a crucial role in minimizing viral transmission and infection. To develop new strategies for preventing SARS-CoV-2 infection, this study aimed to identify proteins that protect against viral infection in saliva. We collected 551 saliva samples from 290 healthcare workers who had tested positive for COVID-19, before vaccination, between June and December 2020. The samples were categorized based on their ability to block or enhance infection using in vitro assays. Mass spectrometry and enzyme-linked immunosorbent assay experiments were used to identify and measure the abundance of proteins that specifically bind to SARS-CoV-2 antigens. Immunoglobulin (Ig)A specific to SARS-CoV-2 antigens was detectable in over 83% of the convalescent saliva samples. We found that concentrations of anti-receptor-binding domain IgA >500 pg/µg total protein in saliva correlate with reduced viral infectivity in vitro. However, there is a dissociation between the salivary IgA response to SARS-CoV-2, and systemic IgG titers in convalescent COVID-19 patients. Then, using an innovative technique known as spike-baited mass spectrometry, we identified novel spike-binding proteins in saliva, most notably vimentin, which correlated with increased viral infectivity in vitro and could serve as a therapeutic target against COVID-19.