Table 3.
mRNA doses in in vivo prophylactic vaccination. The mRNA dose required to induce neutralizing antibody titers, or the dose that provides protection against viral challenge, is shown for different mRNA delivery systems and in different species. The advent of lipid nanoparticles (LNPs) for mRNA delivery reduced the required doses by ~10-fold compared to earlier delivery systems.
| Delivery System | mRNA Type | Species | Dose | Readout | Reference |
|---|---|---|---|---|---|
| Naked mRNA | non-modified | mouse | 80 µg twice | protection | [140] |
| Naked mRNA | self-amplifying | mouse | 1.25 µg twice | protection | [140] |
| Protamine | non-modified | mouse | 10 µg twice | neutralizing titers | [66] |
| Protamine | non-modified | mouse | 80 µg twice | protection | [66] |
| Modified Dendrimer | self-amplifying | mouse | 40 µg once or 4 µg twice |
neutralizing titers | [126] |
| DOTAP/DOPE/PEG | nucleoside modified | mouse | 12 µg twice intranasal | neutralizing titers and protection | [130] |
| Cationic Nanoemulsion | self-amplifying | mouse | 15 µg twice | neutralizing titers | [70] |
| Nanostructured Lipid Carrier | self-amplifying | mouse | 0.1 µg once | neutralizing titers | [71] |
| LNP (Acuitas) | non-modified | mouse | 0.5 µg twice | neutralizing titer | [69] |
| LNP (MC3) | nucleoside-modified | mouse | 10 µg once or 2 µg twice | protection | [99] |
| LNP (MC3) | nucleoside-modified | mouse | 0.4 µg once | protection | [97] |
| LNP (Acuitas) | nucleoside-modified | mouse | 0.5 µg once | protection | [141] |
| LNP (Acuitas) | nucleoside-modified | mouse | 1 µg twice | neutralizing titers | [49] |
| LNP (Moderna) | nucleoside-modified | mouse | 1 µg twice | neutralizing titers and protection | [45] |
| LNP (Acuitas) | non-modified | mouse | 0.25 µg twice | neutralizing titers | [53] |
| LNP (Translate Bio) | non-modified | mouse | 0.2 µg twice | neutralizing titers | [56] |
| LNP (Arcturus) | self-amplifying | mouse | 2 µg once | neutralizing titers and protection | [58] |
| LNP (Acuitas) | self-amplifying | mouse | 0.1 µg twice | neutralizing titers | [60] |
| LNP (Acuitas) | non-modified | Syrian Hamster | 10 µg twice | protection | [53] |
| LNP (MC3) | nucleoside-modified | ferret | 50 µg once | neutralizing titers | [97] |
| Cationic Nanoemulsion | self-amplifying | non-human primate | 75 µg twice | neutralizing titers | [70] |
| LNP (MC3) | nucleoside-modified | non-human primate | 200 µg twice | neutralizing titers | [97] |
| LNP (MC3 or Moderna Lipid H) | nucleoside-modified | non-human primate | 5 µg twice | neutralizing titers | [42] |
| LNP (Acuitas) | nucleoside-modified | non-human primate | 30 µg twice | neutralizing titers | [49] |
| LNP (Moderna) | nucleoside-modified | non-human primate | 100 µg twice | neutralizing titers | [45] |
| LNP (Translate Bio) | non-modified | non-human primate | 15 µg twice | neutralizing titers | [56] |