Abstract

Background. COVD-19 vaccination induces a strong systemic but a weak mucosal immune response in adults. Little is known about the mucosal immune response in children infected or vaccinated against SARS-CoV-2. Aim. To investigate children?s mucosal immune response to SARS-CoV-2 vaccination compared to natural infection. Methods. We enrolled children who received the BNT162b2, Pfizer/BioNTech vaccine at Policlinico Umberto I, Rome, Italy, from Feb to Apr 2022. Saliva samples were collected before the first vaccine dose while 10 days after the second dose both saliva and serum. We also collected serum and saliva from children never vaccinated who tested positive by PCR to SARS-CoV-2 two weeks after the test, between Oct 2020 and Mar 2021. Salivary Spike specific IgA were detected by ELISA test. We further dissected IgA immune response in children by detecting RBD-specific IgA1 (representative of systemic immune response) and RBD-specific IgA2 (representative of mucosal immune response). Results. We enrolled 100 vaccinated children and 41 infected children (aged 5-11 years). Serum Spike-specific IgA were significantly higher in vaccinated children compared to naturally infected children (p=0.008 and p<0.0001 respectively. 28% of children had detectable salivary IgA2 against SARS-CoV-2 even before vaccination, suggesting that in children SARS-CoV-2 infection may be undiagnosed. After vaccination, salivary specific IgA1 significantly increased (p=0.0001). Conversely, infected children had significantly higher salivary RBD-IgA2 compared to IgA1 (p<0.0001).Conclusions. Our results indicate that infection but not vaccination induces a specific mucosal immune response in children.