We recently reported that SARS-CoV-2 infection triggers robust, persistent adaptive immune responses in the tonsils and adenoids of children. However, whether mRNA vaccination induces similar immune responses and how this compares to natural infection in children are unknown. To evaluate these questions, we collected peripheral blood (PBMCs), tonsils, and adenoids from 30 children undergoing tonsillectomy/adenoidectomy primarily in 2022. From questionnaires and serology, we identified 12 vaccinated subjects who had not been infected and compared them to 24 COVID-19 convalescent children from our previous study collected in 2020–2021. We found SARS-CoV-2-specific germinal center and CD27 +switched memory B (B SM) cells, including cells recognizing the spike protein receptor binding domain (RBD) of the original WA-1 strain and RBD from Omicron, in pharyngeal tissues of vaccinated children. PBMCs trended towards having higher percentages of S1 +RBD +B cells post-vaccination than post-infection, while adenoids had more S1 +RBD +B cells post-infection. SARS-CoV-2-specific B SMcells were dominated by IgG isotypes in all tissues, but a higher proportion of IgA +cells were seen post-infection. Furthermore, S1 +RBD +B SMcells showed greater CXCR3 expression post-infection in all tissues. In contrast, S1 +RBD +B SMcells showed higher expression of activation and atypical markers post-vaccination, particularly in PBMCs, implying different characteristics of B cell memory depending on the type of exposure. Our results demonstrate tissue-specific immunity to SARS-CoV-2 in the upper respiratory tract of children after vaccination and provide further evidence that mRNA vaccination induces broad protective B cell memory.

This work was supported in part by intramural funds of NIAID, NIH.