 
        Self-replicating RNA viruses and examples of preclinical studies on infectious diseases
| Delivery method | Indication | Outcome | Reference | 
|---|---|---|---|
| Recombinant particles | |||
| VSV-CHIKV-Env/ZIKV-ME | CHIKV | Protection against CHIKV in mice | [42] | 
| VSV-CHIKV-Env/ZIKV-ME | ZIKV | Protection against CHIKV in mice | [42] | 
| VEE-E2/E3 FCSdel | VEE | Full protection in mice & macaques | [43] | 
| WEE-E2/E3 FCSdel | WEE | Protection in mice, partial protection in macaques | [43] | 
| EEE-E2/E3 FCSdel | EEE | Full protection in mice | [43] | 
| MV-CHIKV C/Env | CHIKV | Viremia protection in macaques | [44] | 
| VSV-LASV-GPC | LHF | Protection in guinea pigs & macaques | [45] | 
| MV-LASV-GPC | LHF | Protection in macaques | [46] | 
| YFV-LASV-GPC | LHF | Protection in guinea pigs | [47] | 
| YFV-LASV-GPC | LHF | Failure to protect marmosets | [48] | 
| VEE-LASV-GPC/LASV-N | LHF | Protection in guinea pigs | [49] | 
| VEE-LASV-GPC | LHF | Protection in inbred CBA/J mice | [50] | 
| VEE-EBOV-G | EVD | Protection in guinea pigs | [49] | 
| KUN-EBOV-G D637L | EVD | Protection in 75% of primates | [51] | 
| VSV-EBOV-G | EVD | Protection against EBOV-Makuna | [52] | 
| VSV-EBOV-G | EVD | Protection against ZEBOV | [53] | 
| VEE-DENV-E85 | DF | Protection against DENV in mice | [54] | 
| MV-DENV-ED3 | DF | Partial protection in mice | [55] | 
| MV-ZIKV-E (MV-E2) | ZIKV | Protection against lethal ZIKV in mice | [56] | 
| MV-E2 + MV-NIS | ZIKV | ZIKV clearance from reproductive tract | [56] | 
| MV-HIV-1 Gag gp160 | HIV/AIDS | Strong cellular & humoral response | [57] | 
| SFV-HIV Env | HIV/AIDS | Superior response to conDNA, recEnv | [58] | 
| SFV-HIV-Env-Gag-Pol-RT | HIV/AIDS | Superior compared to RNA replicons | [59] | 
| MV AIK-C IFVA-HA | Influenza | Protection in cotton rats | [60] | 
| VSVΔG IFVA-HA/NA | Influenza | Protection in mice | [61] | 
| VSV IFVA-HAfl | Influenza | 100% protection after single dose | [62] | 
| VEE IFVA-HA | Influenza | Protection against IFVA in chickens | [63] | 
| SIN-E2S1-M2e | Influenza | 100% protection in mice | [64] | 
| CSFV-IFVA-HA + N | Influenza | Superior immunogenicity to replicon RNA | [65] | 
| VEE-SARS-CoV S | SARS | Protection against SARS in mice | [67] | 
| VSVΔG MERS-CoV S | MERS | Neutralizing Ab and T-cell responses | [68] | 
| MV-SARS-CoV-2 S | COVID-19 | Th1-biased Ab and T-cell responses | [69] | 
| VSV-SARS-CoV-2 S | COVID-19 | Neutralizing Abs, protection in mice | [70] | 
| VSVΔG-SARS-CoV-2 S | COVID-19 | Protection in Syrian golden hamsters | [71] | 
| SIN-SARS-CoV-2 S + αOX40 | COVID-19 | Protection against SARS-CoV-2 in mice | [72] | 
| BVDV-PEDV S | PEDV | PEDV specific Abs, neutralization of PEDV | [73] | 
| Attenuated virus | |||
| YFV (CYD-TDV) | DF | Good safety, no toxicity concerns | [74] | 
| CHIKV-NoLS RNA-LNP | CHIKV | Local protection against CHIKV in mice | [75] | 
| VEE-RABV-G | RABV | Protection against RABV in mice | [76] | 
| RNA replicons | |||
| VEE-ZIKV-ME | ZIKV | Protection in mice with 10 ng RNA | [78] | 
| SFV-HIV-Env-Gag-Pol-Rev | HIV/AIDS | Inferior compared to SFV particles | [59] | 
| SFV-HIV Env | HIV/AIDS | Env-specific Abs in 80% of mice | [79] | 
| VEE-HIV-1 gp140 | HIV/AIDS | Improved RNA stability in mice | [80] | 
| VEE-HIV-1 gp140 | HIV/AIDS | Superior to VEE particles, rec Env | [81] | 
| CSFV-IFVA-HA/N | Influenza | Inferior to CSFV particles | [65] | 
| CSFV-IFVA-HA/N-PEI | Influenza | PEI formulation superior to naked RNA | [65] | 
| SFV-IFVA HA | Influenza | Protection against IFVA in mice | [82] | 
| SFV-IFVA-HA | RSV | Protection against RSV in mice | [82] | 
| SFV-IFVA-HA | TBEV | Protection against TBEV in mice | [82] | 
| VEE-IFVA-HA | Influenza | 64x less RNA replicon than mRNA needed | [84] | 
| VEE-SARS-CoV-2-LNPs | COVID-19 | Dose-dependent Abs, SARS-CoV-2 neutralization | [12] | 
| VEE (LUNAR-COV19) | COVID-19 | Protection in ACE2 transgenic mice | [85] | 
| Plasmid DNA replicons | |||
| VEE V4020 | VEE | Protection against wildtype VEE in mice | [86] | 
| VEE V4020 | VEE | Protection against wildtype VEE in macaques | [87] | 
| SFV-HIV Env/Gag-Pol-Nef | HIV/AIDS | Superior with MVA boost | [88] | 
ACE2: angiotensin-converting enzyme 2; AIDS: acquired immunodeficiency syndrome; αOX40: OX40 immunostimulatory Ab; CHIKV: chikungunya virus; CHIKV-Env: CHIKV E3-E2-6K-E1 Env polyprotein; COVID-19: coronavirus disease 2019; CYD-TDV: chimeric YFV-based tetravalent DENV vaccine; DF: dengue fever; EBOV: Ebola virus; ED3: DENV Env protein domain III; EEE: eastern equine encephalitis virus; EVD: EBOV disease; FCSdel: furin cleavage site deletion; GPC: glycoprotein complex; HAfl: full-length HA; HIV: human immunodeficiency virus; IFVA: influenza virus A; LASV: Lassa fever virus; LHF: Lassa hemorrhagic fever; M2e: M2 protein ectodomain; ME: membrane Env; MERS: Middle East respiratory syndrome; NA: neuraminidase; NIS: sodium iodide symporter; NoLS: nucleolar localization signals; PEDV: porcine epidemic diarrhea virus; PEI: polyethylenimine; RSV: respiratory syncytial virus; SARS: severe acute respiratory syndrome; SARS-CoV-2: SARS-coronavirus-2; WEE: western equine encephalitis virus; ZEBOV: Zaire EBOV; ZIKV: Zika virus
The author contributed solely to the work.
The author declares that he has no conflicts of interest.
Not applicable.
Not applicable.
Not applicable.
Not applicable.
Not applicable.
© The Author(s) 2022.