Understanding the impact of polyethylene glycol (PEG)-lipids on mRNA-LNP vaccine immunogenicity 2260679

Abstract Introduction mRNA - lipid nanoparticle (LNP) vaccines developed against SARS-CoV-2 are a transformative technology and saved millions of lives during the COVID-19 pandemic. In this vaccine platform, LNPs function as both a delivery agent and a powerful adjuvant. However, the relationship between LNP composition and adjuvanticity is not fully understood, hindering future vaccine design. Methods In this study, we focus on the impact of the Polyethylene-glycol conjugated lipid (PEG-lipid) which is one of the four standard lipids used to make LNPs. PEG-lipids are known to give stability to nanoparticles in solution, control particle size, and impact circulation half-life. We designed mRNA-LNP vaccines that encode SARS-CoV-2 spike as a model antigen, and we modulate the amount of PEG-lipid within the LNP. A comparative vaccination study was performed using BALB/c mice. Results We demonstrate that the amount of PEG-lipid used in the LNP formulation has a significant impact on humoral immune responses to mRNA-LNP vaccines in mice and can impact memory B cell responses. Conclusion These findings support the rational design of novel LNPs to create more tailored and effective mRNA vaccines against both existing and emerging infectious pathogens. Funding Source NIAID, R01AI153064 Topic Categories Vaccines and Immunotherapy (VAC)