Salivary IgG Antibody Response to SARS-CoV-2 as a Non-Invasive Assessment of Immune Response—Differences Between Vaccinated Children and Adults

<b>Background</b>: Studies comparing systemic and salivary antibody responses against SARS-CoV-2 between children and adults show conflicting results. Furthermore, it is still unclear whether salivary antibody testing could be a non-invasive approach to evaluate the humoral immune response. <b>Methods</b>: anti-SARS-CoV-2 IgG antibodies were measured in blood and saliva sample pairs from vaccinated adults to investigate whether salivary antibody response could be a non-invasive assessment of immune response. Salivary antibody levels were also compared between vaccinated children and adults to investigate local antibody responses. <b>Results</b>: Salivary IgG antibody response against SARS-CoV-2 largely reflects the systemic response in vaccinated adults. Salivary and systemic antibody concentrations were higher in vaccinated adults who had been infected, received schemes including mRNA-based vaccines, had more exposures, and a shorter time from last exposure. Salivary antibody detection was associated with schemes including mRNA-based vaccines, time from last exposure, and systemic antibody concentrations. Vaccinated children showed higher salivary antibody concentrations than adults. This difference remained when comparing antibody levels between children and adults under equal conditions (vaccination schemes, number of exposures, time from last exposure, COVID-19 history). Younger age, number of exposures, schemes including mRNA-based vaccines, and shorter time from last exposure were associated with salivary antibody levels in a multivariable linear regression analysis (<i>p</i> < 0.0001). <b>Conclusions</b>: Salivary antibody determination against SARS-CoV-2 could be a non-invasive assessment of the short-term immune response in adults with multiple exposures. Furthermore, the stronger salivary antibody response in children suggests that local immune protection may differ between children and adults, contributing to different outcomes.