Evaluation of lipid nanoparticle adjuvants with different PEG lipid ratios and phospholipid modifications in...

Lipid nanoparticles (LNPs) used in mRNA vaccines possess adjuvant activity, but little is known about the composition-function relationships that drive their adjuvanticity. Recent studies demonstrated that, in addition to the ionizable lipids, the type of phospholipids and the ratio of polyethylene glycol (PEG) lipids in LNPs also influence the magnitude and quality of vaccine-induced immune responses. Here we evaluated the cellular and humoral immunity elicited by LNPs with different phospholipids and PEG lipid ratios in cynomolgus macaques. We observed differences in antibody and CD4⁺ T cell responses across LNP groups, although not all comparisons reached statistical significance, likely due to the limited sample size. While this study was exploratory, the findings differed from those previously obtained with these LNPs in mice, confirming the importance of assessing LNP formulations in non-human primates prior to clinical evaluation.