Impact of lipid nanoparticle size on mRNA vaccine immunogenicity

JOURNAL OF CONTROLLED RELEASE

卷:335

Article

Hassett, Kimberly J.¹  Higgins, Jaclyn¹  Woods, Angela¹  Levy, Becca^1,2  Xia, Yan¹  Hsiao, Chiaowen Joyce¹  Acosta, Edward¹  Almarsson, Orn^1,3  Moore, Melissa J.¹  Brito, Luis A.¹ 

[1] Moderna Inc, 200 Technol Sq, Cambridge, MA 02139 USA

[2] Rheos Med, 245 First St Suite 200, Cambridge, MA 02142 USA

[3] Lyndra Therapeut, 65 Grove St Suite 301, Watertown, MA 02472 USA

关键词: Vaccine;    Nanoparticle;    mRNA;    Size;    Lipid;   

DOI  :  10.1016/j.jconrel.2021.05.021

来源: Elsevier

【 摘 要 】

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).

【 授权许可】

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