Salivary Antibody Responses to Two COVID-19 Vaccines following Different Vaccination Regimens

Background: To date, little is known about the salivary mucosal immune response following different COVID-19 vaccine types or after a booster (3rd) dose of the BNT162b2 (BNT) vaccine. Methods: A total of 301 saliva samples were collected from vaccinated individuals and arranged into two cohorts: cohort 1 (n = 145), samples from individuals who had received two doses against SARS-CoV-2; cohort 2 (n = 156), samples from individuals who had received a booster of BNT vaccine. Cohorts 1 and 2 were sub-stratified into three groups based on the types of first and second doses (homologous BNT/BNT, homologous ChAdOx1/ChAdOx1, or heterologous BNT/ChAdOx1vaccinations). Salivary immunoglobulin G (IgG) response to SARS-CoV-2 spike glycoprotein was measured by ELISA, and clinical demographic data were collected from hospital records or questionnaires. Results: Salivary IgG antibody responses against different vaccines, whether homologous or heterogeneous vaccination regimens, showed similar levels in cohorts 1 and 2. Compiling all groups in cohort 1 and 2 showed significant, albeit weak, negative correlations between salivary IgG levels and time (r = -0.2, p = 0.03; r = -0.27, p = 0.003, respectively). In cohort 2, the durability of salivary IgG after a booster dose of BNT162b2 significantly dropped after 3 months compared to the <1 month and 1-3 months groups. Conclusions: Different COVID-19 vaccine types and regimens elicit similar salivary anti-SARS-CoV-2 IgG with modest waning over time. Boosting with BNT162b2 vaccine did not produce an evident increase in mucosal IgG response whereby COVID-19 recovered subjects show higher salivary IgG than naive, post-vaccination subjects. The ChAdOx1/ChAdOx1 regimen showed better correlation between salivary IgG levels and durability. These findings highlight the importance of developing oral or intra-nasal vaccines to induce stronger mucosal immunity.