Mucosal vaccination with long-form TSLP induces migratory cDC1-mediated adaptive immunity against SARS-CoV-2 infection

Adjuvants are indispensable components of subunit vaccines, and the development of adjuvants capable of inducing powerful systemic and mucosal immune responses is critical for enhancing the efficacy of viral vaccines. This study reveals that the human long-form thymic stromal lymphopoietin (lfTSLP) induces antigen-specific systemic IgG and mucosal IgA antibody production with sustained immunogenicity. Mechanistically, lfTSLP enhances germinal center reactions by preferentially activating migratory type 1 conventional dendritic cells (cDC1s). These findings uncover a previously unrecognized mechanism underlying the adjuvant activity of lfTSLP, which enhances vaccine-induced adaptive immunity and confers protection against SARS-CoV-2 infection. These findings indicate that the application of lfTSLP as an adjuvant should be encouraged in the rational design and development of viral vaccines.