Impact of lipid nanoparticle size on mRNA vaccine immunogenicity

作者：Kimberly J. Hassett, Jaclyn S. Higgins, Angela L. Woods, Becca R. Levy, Yan Xia, Chiaowen Joyce Hsiao, Edward P. Acosta, Örn Almarsson, Melissa J. Moore, Luis A. Brito · 发表于：Journal of Controlled Release · 年份：2021 · DOI：10.1016/j.jconrel.2021.05.021 · 被引用次数：365 · 研究领域：RNA Interference and Gene Delivery、Immunotherapy and Immune Responses、SARS-CoV-2 and COVID-19 Research

Lipid nanoparticles (LNP) are effective delivery vehicles for messenger RNA (mRNA) and have shown promise for vaccine applications. Yet there are no published reports detailing how LNP biophysical properties can impact vaccine performance. In our hands, a retrospective analysis of mRNA LNP vaccine in vivo studies revealed a relationship between LNP particle size and immunogenicity in mice using LNPs of various compositions. To further investigate this, we designed a series of studies to systematically change LNP particle size without altering lipid composition and evaluated biophysical properties and immunogenicity of the resulting LNPs. While small diameter LNPs were substantially less immunogenic in mice, all particle sizes tested yielded a robust immune response in non-human primates (NHP).