Molecular therapy. Nucleic acidsJul 28, 2026

Testing lipid nanoparticle vaccine helpers with different PEG and phospholipid types in primates

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Aug 3, 2026

Abstract

Differences in immune responses were observed among lipid nanoparticles (LNPs) with varying phospholipids and polyethylene glycol (PEG) lipid ratios in cynomolgus macaques.

Antibody and CD4⁺ T cell responses varied across different LNP formulations.
Not all observed differences in immune responses reached statistical significance, likely due to a limited sample size.
The findings in macaques diverged from previous studies conducted in mice.
This exploratory evaluation highlights the necessity of testing LNP formulations in non-human primates before progressing to clinical trials.

Simplified

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.

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Funding

Competing interests

N.P. is named on patents describing the use of nucleoside-modified mRNA in LNPs as a vaccine platform. M.R.B. is named on patents describing the use of ligand-targeted nucleoside-modified mRNA in LNPs for lymphocyte targeted therapeutics. They each have disclosed those interests fully to the University of Pennsylvania, and have in place approved plan for managing any potential conflicts arising from licensing of those patents. N.P. served on the mRNA strategic advisory board of Sanofi Pasteur in 2022, Pfizer in 2023–2024 and AldexChem in 2023–2025. N.P. is a member of the Scientific Advisory Board of BioNet and has consulted for Vaccine Company Inc., Pasture Bio and Piezo Therapeutics. M.R.B. served on the advisory board of Capstan Therapeutics in 2024–2025 and Interius Biotherapeutics in 2021–2025. Z.L. held consulting positions at ATGandCo Biotechnology Ltd. and SeqOmics Biotechnology Ltd. when the study was conceived, but neither company contributed to the funding, design, or execution of the research, nor to the preparation of the manuscript. J.H. and K.L. are employees of Genevant Sciences Corporation (GSC) as noted in the author affiliations and own shares or options in the company. Genevant Sciences holds patents and patent applications related to the LNP technology used in this study.

PubMed

Testing lipid nanoparticle vaccine helpers with different PEG and phospholipid types in primates

Abstract

Full Text

Funding

Competing interests

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