MAIT cells activate dendritic cells to promote TFH cell differentiation and induce humoral immunity

Protective immune responses against respiratory pathogens, such as severe acute respiratory syndrome co-ronavirus 2 (SARS-CoV-2) and influenza virus, are initiated by the mucosal immune system. However, most licensed vaccines are administered parenterally and are largely ineffective at inducing mucosal immunity. The development of safe and effective mucosal vaccines has been hampered by the lack of a suitable mucosal adjuvant. In this study we explore a class of adjuvant that harnesses mucosal-associated invariant T (MAIT) cells. We show evidence that intranasal immunization of MAIT cell agonists co-administered with protein, including the spike receptor binding domain from SARS-CoV-2 virus and hemagglutinin from influenza virus, induce protective humoral immunity and immunoglobulin A production. MAIT cell adjuvant activity is mediated by CD40L-dependent activation of dendritic cells and subsequent priming of T follicular helper cells. In summary, we show that MAIT cells are promising vaccine targets that can be utilized as cellular adjuvants in mucosal vaccines.

Automated summary

Protective immune responses against respiratory pathogens largely depend on mucosal immunity, but most licensed vaccines fail to induce sufficient mucosal immunity. A suitable mucosal adjuvant has been lacking for the development of safe and effective mucosal vaccines. This study explores the use of mucosal-associated invariant T (MAIT) cells as adjuvants, showing that intranasal immunization with MAIT cell agonists and viral proteins can induce protective humoral immunity and IgA production.