Table 12.
Self-amplifying RNA vaccines for infectious and cancerous diseases.
| Vaccine Platform | Disease Target | Antigen | Delivery Platform | Preclinical/Clinical Setting | Immune Response | Ref. |
|---|---|---|---|---|---|---|
| saRNA | Influenza | HA | N/A | Mice | - Induction of similar protective efficacy as a conventional mRNA vaccine but at a 64-fold lower dose | [108] |
| saRNA | Influenza | Nucleoprotein | LNP (DLinDMA:DSPC:cholesterol:PEG-DMG 2000, 40:10:2:48) | Mice | - Antigen expression in muscle cells transferred to APCs is responsible for induction of MHC class-I restricted CD8+ T cells | [109] |
| saRNA | RSV | F | LNP (DLinDMA:DSPC:cholesterol:PEG-DMG 2000, 40:10:2:48) | Mice | - Enhanced immunogenicity by activation of type I IFN response | [110] |
| saRNA | Melanoma Colon carcinoma | IL-2 | LNP (DOTAP:DSPC: cholesterol:PEG2000, 40:10:48:2) | Mice | - Induction of immunogenic cancer death, stimulation of TLR3-mediated type I IFN response, priming systemic and memory antitumor immunity - Eradication of large tumors and regression of distal uninjected tumors |
[111] |
| saRNA with mutated VEEV backbone | Melanoma | IL-2 | LNP (DOTAP:DSPC:cholesterol:DSPE-PEG2000, 40:10:48:2) | Mice | - Enhanced intra-tumoral antigen expression by 5.5-fold - Increased CD8+ T cell response - Inhibition of tumor growth |
[112] |
| saRNA | HIV-1C | gag, env, polRT | N/A | Mice/ Phase I (NCT03639714) | - Activation of CD4+ and CD8+ T cells - Production of HIV-1C specific antibodies |
[113] |
| saRNA | Zika | prM, E | N/A | Mice/ Phase II (NCT03953235) | - Moderate humoral and cellular immune responses due to type I IFNs | [114] |
| saRNA | Ebola, H1N1, Toxoplasma gondii | EBOV-GP, HA, cytoplasmic ovalbumin | Dendritic NPs | Mice | - Activation of CD8+ T-cell and antibody responses that fully protected against lethal exposures to the deadly pathogens | [115] |
| saRNA | Zika | E | Dendritic NPs | Mice | - Production of E-specific IgG antibodies - Activation of CD8+ T cells |
[116] |
| saRNA | HIV-1 | TV1 Env gp140 | Cationic nanoemulsion | Rhesus macaques | - Induction of potent cellular responses greater in magnitude than those induced by saRNA packaged in viral replicon particle (VRP) or by a recombinant HIV envelope protein formulated with MF59 adjuvant - Production of anti-envelope binding and neutralizing antibodies that exceeded those induced by VRP vaccine |
[117] |
| saRNA | Influenza | HA | Cationic nanoemulsion | Mice Ferrets |
- Induction of potent neutralizing antibody and cellular immune responses - Protection of immunized animals from lethal viral challenge and containment of viral replication in upper respiratory tract |
[118] |
| saRNA + GM-CSF | Influenza | Nucleoprotein | Cationic nanoemulsion | Mice | - Enhanced recruitment of APCs - Improved magnitude of nucleoprotein-specific CD8+ T-cell response - Improved protection against lethal challenge |
[119] |
| saRNA | Zika | C, prM, E | Cationic nanoemulsion | Mice Non-human primates | - Production of potent neutralizing antibodies - Protection of animals from Zika lethal challenge |
[120] |
| saRNA | HIV | gp120 | LNP (DOTAP:DSPC:cholesterol:DSPE-PEG, 40:10:48:2) | Mice | - Effective delivery in the muscle and expression of mRNA for 30 d - Production of high titers of gp120-specific antibodies and antigen-specific GC B cells |
[121] |
| saRNA | Influenza | Nucleoprotein | LNP (DLinDMA:DSPC:cholesterol:PEG-DMG 2000, 40:10:2:48) | Mice | - Activation of robust polyfunctional CD4+ T helper 1 cells, nucleoprotein-specific cytotoxic CD8+ T cells - Reduced lung viral titers and pathology, and increased survival |
[122] |
| saRNA | Zika | NS3 | LNP (Proprietary lipids) | Mice | - Failure to stimulate antibody production - Production of polyfunctional CD8+ T cells that prevented death in lethally infected adult mice and fetal growth restriction in infected pregnant mice |
[123] |
| saRNA | Rabies | Glycoprotein G | Cationic nanoemulsion | Rat/ Phase I (NCT04062669) | - RNA detectable at injection site and in lymph nodes up to 2 months post-injection - Well tolerated by animals upon intramuscular administration |
[124] |
| taRNA | Influenza | HA | N/A | Mice | - Induction of neutralizing antibodies and a protective immune response at low doses of 50 ng | [125] |
| saRNA | SARS-CoV-2 | S | LNP (ionizable lipid: phosphatidylcholine: cholesterol:PEG-lipid, 50:10:38.5:1.5) | Mice/ Phase I/II (ISRCTN17072692) | - Induction of highly specific Th1-biased neutralizing antibodies and cellular responses | [126] |
| saRNA | SARS-CoV-2 | S | LION | Mice, Non-human primates/ Phase I (NCT04844268) | Low dose of 50 µg: - Production of Th1-biased S-specific IgG antibodies that lasted for 70 d and efficiently neutralized SARS-CoV-2 - Induction of potent T cell response in young mice and nonhuman primates, and induction of both humoral and cellular immunities in aged mice after booster dose High dose of 250 µg: - Induction of neutralizing antibodies that protected non-human primates from infection and disease |
[127] |
| saRNA | SARS-CoV-2 | S | LNP (ionizable lipid:DSPC:cholesterol:PEG2000-DMG, 50:13:35.5:1.5) | hACE2 transgenic mice/ Phase I (NCT04480957) | - Activation of strong Th1-biased antibody responses with neutralizing antibody titers lasting 60 d - Induction of a strong CD8+ T cell response - Protected of mice from mortality and infection |
[128] |