Comparison of levels of nasal, salivary, and plasma antibody to SARS-CoV-2 during natural infection and after vaccination


 
 
 Most studies of immunity to SARS-CoV-2 measure antibody or cellular responses in blood; however, the virus infects mucosal surfaces in the nose and conjunctivae and infectious virus is rarely if ever present in the blood.
 
 
 
 We measured SARS-CoV-2 antibody levels in the plasma, nose, and saliva of infected persons and vaccine recipients using luciferase immunoprecipitation assays. These assays measure antibody that can precipitate the SAR-CoV-2 spike and nucleocapsid proteins.
 
 
 
 Levels of plasma anti-spike antibody declined less rapidly than anti-nucleocapsid antibody in infected persons. SARS-CoV-2 anti-spike antibody levels in the nose declined more rapidly than antibody levels in the blood after vaccination of infected persons. Vaccination of previously infected persons boosted anti-spike antibody in plasma more than in the nose or saliva. Nasal and saliva anti-spike antibody levels significantly correlated with plasma antibody in infected persons who had not been vaccinated and after vaccination of uninfected persons.
 
 
 
 Persistently elevated SARS-CoV-2 antibody in plasma may not indicate persistence of antibody at mucosal sites such as the nose. The strong correlation of SARS-CoV-2 antibody in the nose and saliva with that in the blood suggests that mucosal antibodies are derived primarily from transudation from the blood rather than local production. While SARS-CoV-2 vaccine given peripherally boosted mucosal immune responses in infected persons, the increase in antibody titers were higher in the plasma than at mucosal sites. Taken together, these observations indicate the need for development of mucosal vaccines to induce potent immune responses at sites where SARS-CoV-2 infection occurs.
