Immunogenicity of lipid nanoparticles and its impact on the efficacy of mRNA vaccines and therapeutics

Abstract

Several studies have utilized a lipid nanoparticle delivery system to enhance the effectiveness of mRNA therapeutics and vaccines. However, these nanoparticles are recognized as foreign materials by the body and stimulate innate immunity, which in turn impacts adaptive immunity. Therefore, it is crucial to understand the specific type of innate immune response triggered by lipid nanoparticles. This article provides an overview of the immunological response in the body, explores how lipid nanoparticles activate the innate immune system, and examines the adverse effects and immunogenicity-related development pathways associated with these nanoparticles. Finally, we highlight and explore strategies for regulating the immunogenicity of lipid nanoparticles. Drugs consisting of mRNA encapsulated in lipid nanoparticles (LNP), such as the vaccines developed for COVID-19, are poised to have a massive impact in future therapy, but researchers are still learning about their interactions with the immune system. Hyukjin Lee and colleagues at Ewha Womans University, Seoul, South Korea, have reviewed how the formulated RNA/LNP can positively stimulate the immune response to elicit more robust vaccine protection, but also show potential for harm arising from inappropriate or excessive immune activation. The natural response to lipids or foreign RNA may possibly contribute to allergic or even autoimmune conditions. Fortunately, there are strategies for counteracting these adverse effects, including chemical modifications to the RNA, changes in the lipid formulation, or altering the adminiration routes of delivery. More experience with this promising drug class should yield safer and more effective LNP formulations.