Table 7.
LNP-entrapped IVT mRNA vaccines for prevention of viral diseases.
| Vaccine Platform | Disease Target | Antigen | Delivery Platform | Preclinical/ Clinical Setting | Immune Response | Ref. |
|---|---|---|---|---|---|---|
| m1Ѱ IVT mRNA | Zika | prM, E | DMAP-BLP:DSPC: cholesterol: PEG-lipid, 50:10:38.5:1.5 | Mice Non-human primates | - Induction of high neutralizing antibody titers (∼ 1/100 000) | [50,51] |
| m1Ѱ IVT mRNA | Influenza A H7N9, H10N8 | H7, H10 | DMAP-BLP:DSPC: cholesterol: PEG-lipid, 50:10:38.5:1.5 | Mice Ferrets Phase I clinical trial (NCT03076385) | - Promoted HA inhibition and potent neutralizing antibodies - Promoted high seroconversion rates |
[52] |
| m1Ѱ IVT mRNA | Influenza A H10N8 | H10 | DMAP-BLP:DSPC:cholesterol: PEG-lipid:GLA, 50:10:38.5:1.33:0.17 | Non-human primates | - Induction of IFN-polarized innate immunity - Activation of H10-specific T follicular helper cells and robust GC formation in vaccine-draining lymph nodes - Production of sustained HA inhibition antibody titers |
[53,54] |
| m1Ѱ IVT mRNA | Powassan | prM, E of Zika virus | DMAP-BLP:DSPC: cholesterol: PEG-lipid, 50:10:38.5:1.5 | Mice | - Production of high neutralizing antibody titers and sterilizing immunity - Induction of cross-neutralizing antibodies against multiple tick-borne flaviviruses - Protection of mice against Langat virus |
[56] |
| m1Ѱ IVT mRNA | Dengue | NS3, NS4B, NS5 | ionizable lipid:DSPC: cholesterol: PEG-lipid, 50:10:38.5:1.5 | Mice | - Induction of a strong CD8+ T cell response independently of IFN-induced innate immunity - Protection against Dengue infection |
[57] |
| m1Ѱ IVT mRNA | Ebola | gE | DMAP-BLP:DSPC: cholesterol: PEG-lipid, 50:10:38.5:1.5 | Guinea pigs | - Improved vaccine potency mediated by human Igκ signal peptide - Induction of high glycoprotein-specific neutralizing antibody titers - Protection of immunized animals from lethal viral challenge |
[58] |
| m1Ѱ IVT mRNA | HIV-1 | Env 1086C | ionizable lipid: phosphatidylcholine: cholesterol: PEG-lipid, 50:10:38.5:1.5 | Rabbits Rhesus macaques | - Induction of high glycoprotein-specific neutralizing antibody titers and antibody-dependent cellular cytotoxicity | [59] |
| m1Ѱ IVT mRNA | Nipah | Soluble Hendra virus glycoporotein | ionizable lipid: phosphatidylcholine: cholesterol: PEG-lipid, 50:10:38.5:1.5 | Syrian hamsters | - Induction of suboptimal primed immune response - Protection of 70% of immunized animals from lethal viral challenge |
[60] |
| m1Ѱ IVT mRNA | Cytomegalovirus | gB | ionizable lipid: phosphatidylcholine: cholesterol: PEG-lipid, 50:10:38.5:1.5) | Rabbits | - Enhanced durability of antibody responses and increased breadth of gB-specific IgG binding antibodies compared to gB/MF59 - Induction of low magnitude gB-specific T cell immunity |
[61] |
| m1Ѱ IVT mRNA | Cytomegalovirus | gB, pentameric complex, pp65 | ionizable lipid: DSPC:cholesterol: PEG-lipid, 50:10:38.5:1.5 | Mice | - Activation of Th1-biased multi-antigenic T cell responses - Formation of conformation-dependent neutralizing monoclonal antibodies |
[62] |
| m1Ѱ IVT mRNA | HSV-2 | gD2, gC2, gE2 | ionizable lipid: phosphatidylcholine: cholesterol: PEG-lipid, 50:10:38.5:1.5 | Mice | - Enhanced humoral, cellular, and memory responses - Protection against neonatal herpes - Generation of cross-reactive antibodies that neutralized HSV-1 and inhibited viral latency |
[63], [64], [65] |
| m1Ѱ IVT mRNA | VZV | gE | DMAP-BLP:DSPC: cholesterol: PEG-lipid, 50:10:38.5:1.5 | Rhesus macaques | - Induction of similar and favored immunogenicity compared to the adjuvanted protein subunit and the live attenuated vaccine, respectively - Activation of robust humoral and CD4+ T cell responses |
[66] |
| m1Ѱ IVT mRNA | RSV | F | MC3:DSPC: cholesterol: PEG2000-dimyristoylglycerol, 58:30:10:2 | Mice Cotton rats | - Enhanced induction of cellular responses compared to an adjuvanted prefusion stabilized F protein vaccine | [67] |
| m1Ѱ IVT mRNA | RSV | Prefusion stabilized F protein | MC3:DSPC: cholesterol: PEG2000-dimyristoylglycerol, 58:30:10:2 | Phase I clinical trial | - Activation of robust humoral immune responses - Induction of F-specific CD4+-biased cellular immune responses |
[68] |
| m1Ѱ IVT mRNA CV7202 | Rabies | RABV-G | ionizable lipid:DSPC: cholesterol:PEG-lipid, 50:10:38.5:1.5 | Phase I clinical trial (NCT03713086) | - Induction of similar neutralizing and IgG antibody titers to a licensed inactivated rabies vaccine (Rabipur) | [69] |