Research Spotlight: Investigating the Impact of Delivery System Design on the Efficacy of Self-Amplifying RNA Vaccines

"Investigating the Impact of Delivery System Design on the Efficacy of Self-Amplifying RNA Vaccines"

mRNA vaccines are a transformative solution in vaccine technology and have been on full display throughout the ongoing COVID-19 pandemic. These vaccines elicit transient antigen expression. This transient expression is often desirable for its minimal risk of genetic transformation, but also affects mRNA potency and requires a higher dose. This problem is being solved by attempted augmentation of mRNA to include genetic elements that allow self-amplification. This allows self-amplifying mRNA (SAM) vaccines to self-amplify over time, and thus, requires a lower dose than non-self-amplifying vaccines.

SAM needs to be delivered to cells by some carrier that protects it and gets it where it needs to go. Previously, a comparison of four different cationic SAM delivery platforms including liposomes, solid lipid nanoparticles (SLNs), polymeric nanoparticles (NPs), and emulsions, had not been conducted. All of the formulations were prepared using scalable microfluidics manufacturing practices. Liposomes were prepared with lipid mixtures of DOPE and either DOTAP or DDA at 1:1 w/w. SLNs were prepared as a mixture of Tristearin, DOTAP or DDA (1:1 w/w), and DMG-PEG2000. NPs were prepared using a mixture of poly lactide: glycolide (50:50), PLGA, and DOTAP or DDA (1:1 w/w). Emulsions were oil-in-water formulations mixing DOTAP or DDA with squalene. All of the formulations were loaded with SAM-RVG.

In vitro testing of DOTAP and DDA liposomes and DOTAP NPs led to in vivo testing of these formulations. The DOTAP NPs were effective at producing a robust immune response in mice and had a comparative potency to commercially available vaccines Rabipur and the benchmark CNE56. With further optimization, the DOTAP NPs could be a great synthetic alternative delivery platform for SAM vaccines. This investigation paves the way for better delivery platforms of SAM vaccines.

Thank you, Dr. Perrie, for using Avanti's DSPC, DMG-PEG2000, DDA, and DOTAP products in your research. We are excited to see what you uncover in the future!

Click HERE to read this study in its entirety!