Did you know that tweaking just two components of a lipid nanoparticle can dramatically shift the immune response toward either antibody production or CD8+ T cell activation? A recent study, “Tailoring the adjuvanticity of lipid nanoparticles by PEG lipid ratio and phospholipid modifications,” by Norbert Pardi and his team at the University of Pennsylvania, USA, reveals how specific changes in phospholipid identity and PEG-lipid ratio modulate LNP adjuvanticity and immune profile.

Key Findings:

• Lowering PEG-lipid ratio (0.5%) and using DSPC phospholipid enhanced humoral immunity with >3x IgG and virus-neutralizing antibody levels compared to controls at 16 weeks.
• LNPs containing DOPS phospholipid triggered significantly stronger CD8+ T cell responses, essential for cancer vaccine applications.
• The biodistribution, cellular uptake, and inflammatory cytokine profiles explained differences in immune outcomes, highlighting formulation as a lever for vaccine tailoring.

Why It Matters:
This work shifts the paradigm from “one-formulation-fits-all” to a precision-engineered LNP design strategy for mRNA vaccines. Whether the goal is long-lasting antibodies or cytotoxic T cell responses, optimizing PEG and phospholipid components could unlock the next generation of vaccines for infectious diseases and cancer.

Read more: https://www.nature.com/articles/s41565-025-01958-5