Graduate Student West Virginia University Morgantown, West Virginia
Ionizable lipid nanoparticles (LNPs) enable intracellular delivery of mRNA vaccines to immune cells. mRNA vaccines require adjuvants to induce strong cell-mediated immune responses against pathogens and cancer. Toll-like receptor 7 (TLR7) adjuvants induce type I interferons and proinflammatory cytokines for immune responses. However, intracellular delivery of TLR7 adjuvants remains challenging. Ionizable LNPs can encapsulate mRNA vaccines and hydrophobic adjuvants. CL347 is a potent adjuvant that stimulates the TLR7 receptor. We developed adjuvanted ionizable LNPs with SM102 and CL347 as the ionizable lipid and TLR7 adjuvant, respectively. CL347-SM102 LNPs showed sizes below 150 nm with spherical morphology and mRNA encapsulation efficiency above 95%. In vivo studies demonstrated increased IFN-γ producing CD4 and CD8 T cells in mice immunized with adjuvanted LNPs versus non-adjuvanted LNPs. Human PBMCs treated with adjuvanted LNPs showed higher CD40 expression and cytokine secretion. Results suggest ionizable LNPs platform’s potential for delivering mRNA and adjuvants for vaccines.
Learning Objectives:
Articulate the scientific rationale for using adjuvanted ionizable lipid nanoparticles in vaccine delivery.
Explain the formulation strategy behind co-delivering mRNA and TLR7 within a single nanoparticle system.
Identify the role of TLR7 activation in shaping innate and adaptive immune responses.
Describe the immunostimulatory outcomes achieved through this co-delivery approach.
Evaluation of how the combined strategy facilitates enhanced immune responses compared to conventional delivery systems.
