Mucosal unadjuvanted booster vaccines induce de novo IgA responses by conversion of pre-existing immunity 2452

Abstract Description Mucosal delivery of vaccine boosters induces robust local protective immune responses even without any adjuvants. Yet, the mechanisms by which antigen alone induces mucosal immunity in the respiratory tract remain unclear. After intramuscular mRNA-LNP primary immunization, we show that a nasal booster with an unadjuvanted spike protein elicits protective mucosal immunity by retooling the lymph node-resident immune cells. Upon intranasal boosting, memory B cells in peripheral lymph nodes rapidly migrate to the lung, differentiating into antigen-specific IgA-secreting plasma cells. Memory CD4 T cells serve as a natural adjuvant for de novo production of mucosal IgA by inducing chemokines for memory B cell recruitment. Furthermore, CD40 and TGF-b signaling play crucial roles in mucosal IgA development. These findings help explain why nasal boosters do not require an adjuvant to induce robust mucosal immunity in the respiratory mucosa and can be used to design safe and effective vaccines against respiratory pathogens. Topic Categories Mucosal and Regional Immunology (MUC)