Thermostable, self-amplifying formulations

saRNA borrows the replicase of an alphavirus. Once in the cytoplasm it copies itself, so antigen expression rises for days and a microgram-scale dose can match a much larger mRNA dose.

saRNA molecules are roughly 9 to 12 kb, several times longer than a typical mRNA. They need carriers with higher encapsulation capacity and gentle mixing that does not shear the RNA.

Circular RNA lacks free ends, resists exonucleases and gives prolonged expression without self-replication, making it a third option between mRNA and saRNA.

Route of administration shapes the response. Intramuscular delivery favours systemic antibodies; intranasal delivery can build mucosal IgA and resident memory T cells at the site of infection.

Ligands such as mannose or anti-CD40 antibodies bias delivery towards dendritic cells and improve cross-presentation to CD8 T cells.

For tolerance, the same particle without adjuvant and carrying an autoantigen can promote regulatory T cells instead of effector responses.

Vaccine carriers are judged on the same attributes as any biologic product: consistent particle size, encapsulation efficiency, lipid identity and low endotoxin, batch after batch.

Lyophilised presentation, room-temperature stability for at least a week and compatibility with existing fill-finish lines decide whether a formulation can be distributed outside well-resourced settings.