Self-replicating RNA viruses and examples of preclinical studies on infectious diseases

Delivery methodIndicationOutcomeReference
Recombinant particles
VSV-CHIKV-Env/ZIKV-MECHIKVProtection against CHIKV in mice[42]
VSV-CHIKV-Env/ZIKV-MEZIKVProtection against CHIKV in mice[42]
VEE-E2/E3 FCSdelVEEFull protection in mice & macaques[43]
WEE-E2/E3 FCSdelWEEProtection in mice, partial protection in macaques[43]
EEE-E2/E3 FCSdelEEEFull protection in mice[43]
MV-CHIKV C/EnvCHIKVViremia protection in macaques[44]
VSV-LASV-GPCLHFProtection in guinea pigs & macaques[45]
MV-LASV-GPCLHFProtection in macaques[46]
YFV-LASV-GPCLHFProtection in guinea pigs[47]
YFV-LASV-GPCLHFFailure to protect marmosets[48]
VEE-LASV-GPC/LASV-NLHFProtection in guinea pigs[49]
VEE-LASV-GPCLHFProtection in inbred CBA/J mice[50]
VEE-EBOV-GEVDProtection in guinea pigs[49]
KUN-EBOV-G D637LEVDProtection in 75% of primates[51]
VSV-EBOV-GEVDProtection against EBOV-Makuna[52]
VSV-EBOV-GEVDProtection against ZEBOV[53]
VEE-DENV-E85DFProtection against DENV in mice[54]
MV-DENV-ED3DFPartial protection in mice[55]
MV-ZIKV-E (MV-E2)ZIKVProtection against lethal ZIKV in mice[56]
MV-E2 + MV-NISZIKVZIKV clearance from reproductive tract[56]
MV-HIV-1 Gag gp160HIV/AIDSStrong cellular & humoral response[57]
SFV-HIV EnvHIV/AIDSSuperior response to conDNA, recEnv[58]
SFV-HIV-Env-Gag-Pol-RTHIV/AIDSSuperior compared to RNA replicons[59]
MV AIK-C IFVA-HAInfluenzaProtection in cotton rats[60]
VSVΔG IFVA-HA/NAInfluenzaProtection in mice[61]
VSV IFVA-HAflInfluenza100% protection after single dose[62]
VEE IFVA-HAInfluenzaProtection against IFVA in chickens[63]
SIN-E2S1-M2eInfluenza100% protection in mice[64]
CSFV-IFVA-HA + NInfluenzaSuperior immunogenicity to replicon RNA[65]
VEE-SARS-CoV SSARSProtection against SARS in mice[67]
VSVΔG MERS-CoV SMERSNeutralizing Ab and T-cell responses[68]
MV-SARS-CoV-2 SCOVID-19Th1-biased Ab and T-cell responses[69]
VSV-SARS-CoV-2 SCOVID-19Neutralizing Abs, protection in mice[70]
VSVΔG-SARS-CoV-2 SCOVID-19Protection in Syrian golden hamsters[71]
SIN-SARS-CoV-2 S + αOX40COVID-19Protection against SARS-CoV-2 in mice[72]
BVDV-PEDV SPEDVPEDV specific Abs, neutralization of PEDV[73]
Attenuated virus
YFV (CYD-TDV)DFGood safety, no toxicity concerns[74]
CHIKV-NoLS RNA-LNPCHIKVLocal protection against CHIKV in mice[75]
VEE-RABV-GRABVProtection against RABV in mice[76]
RNA replicons
VEE-ZIKV-MEZIKVProtection in mice with 10 ng RNA[78]
SFV-HIV-Env-Gag-Pol-RevHIV/AIDSInferior compared to SFV particles[59]
SFV-HIV EnvHIV/AIDSEnv-specific Abs in 80% of mice[79]
VEE-HIV-1 gp140HIV/AIDSImproved RNA stability in mice[80]
VEE-HIV-1 gp140HIV/AIDSSuperior to VEE particles, rec Env[81]
CSFV-IFVA-HA/NInfluenzaInferior to CSFV particles[65]
CSFV-IFVA-HA/N-PEIInfluenzaPEI formulation superior to naked RNA[65]
SFV-IFVA HAInfluenzaProtection against IFVA in mice[82]
SFV-IFVA-HARSVProtection against RSV in mice[82]
SFV-IFVA-HATBEVProtection against TBEV in mice[82]
VEE-IFVA-HAInfluenza64x less RNA replicon than mRNA needed[84]
VEE-SARS-CoV-2-LNPsCOVID-19Dose-dependent Abs, SARS-CoV-2 neutralization[12]
VEE (LUNAR-COV19)COVID-19Protection in ACE2 transgenic mice[85]
Plasmid DNA replicons
VEE V4020VEEProtection against wildtype VEE in mice[86]
VEE V4020VEEProtection against wildtype VEE in macaques[87]
SFV-HIV Env/Gag-Pol-NefHIV/AIDSSuperior 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