TLR7-Adjuvanted Ionizable Lipid Nanoparticles for mRNA Vaccine Delivery

Area of Science:

• Nanomedicine
• Immunology
• Vaccinology

Background:

• Ionizable lipid nanoparticles (LNPs) are crucial for intracellular mRNA delivery.
• Adjuvants stimulating Toll-like receptor 7 (TLR7) are vital for robust immune responses but face delivery challenges.
• Concurrent delivery of mRNA and adjuvants is needed for effective vaccines.

Purpose of the Study:

• To develop ionizable LNPs for co-delivery of mRNA and a TLR7 adjuvant (CL347).
• To evaluate the physicochemical properties and in vivo efficacy of CL347-SM102 LNPs.
• To assess the immunomodulatory effects of adjuvanted LNPs on immune cells.

Main Methods:

• Formulation of ionizable LNPs incorporating SM102 and CL347.
• Characterization of particle size, morphology, and mRNA encapsulation efficiency.
• In vivo studies in mice to assess T cell responses (IFN-γ).
• In vitro studies with human PBMCs to evaluate CD40 expression and cytokine secretion (IL-6, IFN-γ).

Main Results:

• CL347-SM102 LNPs showed particle size <150 nm, spherical morphology, and >95% mRNA encapsulation.
• Immunization with adjuvanted LNPs resulted in a two-fold increase in IFN-γ producing CD4+ and CD8+ T cells.
• Human PBMCs treated with adjuvanted LNPs displayed significantly higher CD40 expression and pro-inflammatory cytokine secretion.

Conclusions:

• Ionizable LNPs are a promising platform for co-delivering mRNA and small molecule adjuvants.
• The developed CL347-SM102 LNPs effectively enhance cell-mediated immunity.
• This approach holds potential for developing advanced prophylactic and therapeutic vaccines.