Graduate Student Univ. of Pennsylvania Perelman Sch. of Med. Philadelphia, Pennsylvania, United States
Disclosure(s):
Emily Daley: No financial relationships to disclose
Introduction/Rationale: 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.