Lipid nanoparticle SARS-CoV-2 vaccine-mediated immunopeptidome identification 4042

Description The expedient development of mRNA vaccines against SARS-CoV-2 was built upon several decades of work to better understand sub-micron-sized lipid-based particles as tools for drug delivery. Many aspects of these lipid nanoparticles (LNPs) make them ideal for delivery of mRNA in the context of vaccines, all of which can be tuned by lipid selection. Early work with any lipid formulation typically focuses on in vitro and in vivo expression of protein from the transcript cargo. However, it is also of vital importance how the protein resulting from LNP transfection is presented on MHC, as this will impact the type and magnitude of the immune response to the antigen. In this study, LNPs encoding SARS-CoV-2 Spike protein were formulated with several different lipids proposed to stimulate immune responses. These LNPs were used to transfect human monocyte-derived dendritic cells and Spike-derived MHC class I and class II peptides were identified. Evaluation of immunopeptidomic differences between these formulations as well as understanding of resulting immune responses will help design of vaccine LNPs in the future.