Antigen-Specific mRNA–LNP Vaccination with mTOR Inhibition Promotes Treg Cells and Limits Allergy

While allergen-encoded mRNA-lipid nanoparticle (mRNA-LNP) vaccine elicits Th1 and cytotoxic CD8+ T responses that counterbalance Th2 immunity, co-administration of mRNA-LNP with an mTOR inhibitor shifts this profile by promoting generation of functional regulatory T cells and partially attenuating Th1 and CD8+ T cell responses.

In pre-clinical models of allergic asthma, this combinatorial strategy preserved the anti-allergic effects of mRNA-LNP immunization, reduced eosinophil activation markers, and limited vaccine-associated cytotoxicity. The ability of an mTOR inhibitor to profoundly modify mRNA-LNP vaccination by inducing regulatory T cells presents a potential strategy to enhance regulatory immunity in the treatment of allergy and other inflammatory diseases.