SARS-CoV-2 mRNA vaccination elicits distinct pharyngeal mucosal B cell responses in children compared to infection 3915

Description Tonsils and adenoids are mucosal lymphoid tissues in the upper airway with unique lymphocytes not found in blood. We recently reported that SARS-CoV-2 infection elicits robust, enduring adaptive immune responses in these tissues; whether mRNA vaccination generates immunity in these tissues and how this compares to natural infection remains unknown. In 2022, we identified 10 mRNA COVID-19 vaccinated, uninfected (VAC) children and compared their blood, adenoids and tonsils to samples from 24 COVID-19 convalescent (INF) children recruited in 2020-2021. By high dimensional flowcytometry we found SARS-CoV-2-specific (S+) B cells, in all tissues from both groups. S+ B cells were primarily Ig-switched memory B cells (BSM), yet INF and VAC S+ BSM exhibited differences. Although S+ BSM cells were primarily IgG+ in all tissues, post-INF had higher proportions of IgA+ cells. Single cell BCR clonal analysis revealed S+ B cells expanded more in post-INF pharyngeal tissues. Notably, higher percentages of S+ B cells were CXCR3+CD21+ BSM cells post-INF, while CXCR3-CD21+/- BSM were enriched post-VAC. We further found that tissue derived CXCR3+CD21+ BSM cells had lower surface IgG or IgA, stronger responses to BCR stimulation, and increased plasma cell differentiation than CXCR3-CD21+ BSM, indicating functional differences. Our results show that infection and vaccination lead to distinct B cell memory in the upper airway, providing insight for mucosal immunity and vaccine efficacy. Funding Sources This research was supported by the Division of Intramural Research of NIAID, NIH. Topic Categories Mucosal and Regional Immunology (MUC)