Mucosal antibody responses to SARS-CoV-2 booster vaccination and breakthrough infection

Coronavirus disease 2019 (COVID-19) vaccines have saved millions of lives. However, variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged causing large numbers of breakthrough infections. These developments necessitated the rollout of COVID-19 vaccine booster doses. It has been reported that mucosal antibody levels in the upper respiratory tract, especially for secretory IgA (sIgA), correlate with protection from infection with SARS-CoV-2. However, it is still unclear how high levels of mucosal antibodies can be induced. In this study, we measured serum IgG, saliva IgG, and saliva sIgA responses in individuals who received COVID-19 mRNA booster vaccinations or who experienced breakthrough infections. We found that mRNA booster doses could induce robust serum and saliva IgG responses, especially in individuals who had not experienced infections before, but saliva sIgA responses were weak. In contrast, breakthrough infections in individuals who had received the primary mRNA vaccination series induced robust serum and saliva IgG as well as saliva sIgA responses. Individuals who had received a booster dose and then had a breakthrough infection showed low IgG induction in serum and saliva but still responded with robust saliva sIgA induction. These data suggest that upper respiratory tract exposure to antigen is an efficient way of inducing mucosal sIgA while exposure via intramuscular injection is not.IMPORTANCEAntibodies on mucosal surfaces of the upper respiratory tract have been shown to be important for protection from infection with SARS-CoV-2. Here we investigate the induction of serum IgG, saliva IgG, and saliva sIgA after COVID-19 mRNA booster vaccination or breakthrough infections. Antibodies on mucosal surfaces of the upper respiratory tract have been shown to be important for protection from infection with SARS-CoV-2. Here we investigate the induction of serum IgG, saliva IgG, and saliva sIgA after COVID-19 mRNA booster vaccination or breakthrough infections.