2368. SARS-CoV-2 mRNA vaccination induces B cell immunity in the tonsils and adenoids of children

BACKGROUND: We recently reported that SARS-CoV-2 infection triggered robust adaptive immune responses in the tonsils and adenoids of children. However, whether intramuscular mRNA vaccination induces immunity in these tissues is unknown. METHODS: We collected peripheral blood, tonsils, and adenoids from 21 children undergoing tonsillectomy/adenoidectomy in 2022 who had previously received a COVID-19 mRNA vaccination. From questionnaires and serology, we identified 10 vaccinated subjects who had not been infected; the remaining 11 were both infected and vaccinated. We characterized SARS-CoV-2-specific B cells that bound fluorescently-labelled spike proteins (S1 and RBD) in the blood and tissues of these participants using high dimensional flow cytometry, and compared them to SARS-CoV-2-specific B cells from 24 COVID-19 convalescent children recruited in 2020-2021. RESULTS: We identified SARS-CoV-2-specific B cells (S1(+)RBD(+)) in the blood, tonsils, and adenoids of nearly all infected and vaccinated subjects. Tonsils and adenoids post-infection had a higher percentage of S1(+)RBD(+) memory B cells than post-vaccination, but differences in the percentage of S1(+)RBD(+) cells were not noted in the peripheral blood. Furthermore, we found that only 20% of vaccinated only subjects had SARS-CoV-2-specific germinal center B cells in their tissues compared to over 70% of infected subjects and subjects with hybrid immunity. Unsupervised analyses of the high dimensional flow cytometry data revealed differences in the characteristics of SARS-CoV-2-specific B cells post-vaccination and post-infection; S1(+)RBD(+) B cells from infected subjects had a higher portion of CXCR3(+) and IgA(+) memory B cells, while those from vaccinated subjects had a greater proportion of CD21(lo) memory B cells in the blood and tissues, implying a greater extrafollicular response post-vaccination but stronger mucosal IgA and IFN-γ-induced B cell responses post-infection. CONCLUSION: We found tissue-specific immunity to SARS-CoV-2 in the upper respiratory tract lymphoid tissue after mRNA vaccination, but vaccination induced B cell phenotypes distinct from that of natural infection which may affect the quality and duration of immunity in the blood and at the mucosal surface. DISCLOSURES: Pedro Milanez-Almeida, PhD, Novartis: Salary