Lipid-free, thermostable mRNA vaccines prepared using atomic layer deposition.

Area of Science:

• Vaccinology
• Materials Science
• Biotechnology

Background:

• Lipid nanoparticle (LNP) mRNA vaccines are crucial for combating SARS-CoV-2 and other pathogens.
• Current mRNA-LNP vaccines require sub-zero storage and face manufacturing hurdles due to instability.

Purpose of the Study:

• To develop thermally stable, lipid-free mRNA vaccines.
• To overcome the limitations of current mRNA-LNP vaccine formulations.

Main Methods:

• mRNA was embedded in polysaccharide microparticles via spray-drying.
• Atomic layer deposition (ALD) was used to encapsulate microparticles in alumina shells.
• Vaccines encoded for ovalbumin, N332-GT2 (HIV), and green fluorescent protein (GFP).

Main Results:

• Alumina-coated microparticles with lipid-free mRNA were internalized by macrophages in vitro.
• These vaccines elicited robust immune responses in vivo, outperforming LNP-based mRNA vaccines.
• The novel vaccines demonstrated stability for 6 months at temperatures up to 40 °C.

Conclusions:

• Alumina-coated, lipid-free mRNA vaccines offer a stable and effective alternative to LNP-based formulations.
• This approach addresses current limitations in mRNA vaccine storage and manufacturing.
• The technology may expand the utility of mRNA vaccines against various diseases.