Assessing mucosal antibody responses to SARS-CoV-2 in humans and mice

Abstract COVID-19 is a respiratory disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We previously developed an enzyme-linked immunosorbent assay (ELISA) protocol to profile antibody responses to the SARS-CoV-2 Spike protein and its receptor-binding domain (RBD) in the saliva of patients with COVID-19. Anti-SARS-CoV-2 antibody responses were readily detected in saliva, peaking at 16–30 days post-symptom onset. While anti-SARS-CoV-2 IgM/IgA were found to decay, IgG responses were more long-lived, persisting up to 105 days. Now we wish to know (1) if anti-SARS-CoV-2 antibodies are generated locally in the oral cavity, (2) the relative kinetics of IgA versus IgG appearance in the oral cavity, and (3) whether salivary antibodies have the capacity to neutralize SARS-CoV-2. To answer these, I have adapted our ELISA to detect secretory component-associated SARS-CoV-2-specific antibodies. I found that 33.3% and 26.9% of COVID-19 patients were positive for secretory component-associated antibodies to Spike and RBD, respectively. Secretory component-associated antibodies correlated with antigen-specific IgA levels, particularly for the Spike antigen. Moreover, using saliva from contact-traced subjects, I found that anti-Spike/RBD IgM/IgA are detected in the saliva 7 days post-exposure, prior to IgG. Lastly, I detected Spike-specific antibody-secreting cells in lymphoid tissues draining the upper respiratory tract upon intranasal infection of K18-hACE2 mice with a non-lethal dose of SARS-CoV-2. In summary, I have provided evidence in humans and mice that a local antibody response that quickly class switches to IgA occurs in the oral cavity and draining lymph nodes upon infection with SARS-CoV-2.