Mucosal immune responses to SARS-CoV-2 infection and COVID-19 vaccination

SARS-CoV-2 continues to circulate in the community. We hypothesise that mucosal immunity is required to prevent continuing viral acquisition and transmission. Objectives: To determine whether SARS-CoV-2 infection or vaccination elicits specific neutralising antibodies in saliva, and to assess the longevity of protection. Methods: Initially, 111 COVID-19 convalescent participants were recruited, 11-369 days after diagnosis. Saliva and blood samples were assayed for antibodies specific for Spike protein, Receptor Binding Domain and Nucleoprotein. In a second cohort, 123 participants were recruited. Saliva and serum antibodies to the same antigens were assayed before and after their first and second COVID-19 vaccinations, with 150 day follow up. Results: Natural infection induces and boosts IgA and IgG in oral fluid and serum; vaccination does not induce or boost specific saliva IgA; IgG can be found in saliva after vaccination, but only when serum IgG concentrations are high; IgA is important for SARS-CoV-2 neutralisation activity by oral fluid, but there can also be contributions from serum IgG and other factors. Conclusions: New COVID-19 vaccines should target both systemic and mucosal immunity, to establish a first line of immune defence at the mucosal barrier. This would benefit vulnerable patient populations and may help to eradicate SARS-CoV-2 circulation.