Replicon RNA Viral Vectors as Vaccines
Abstract
:1. Introduction
2. Self-Replicating RNA Expression Systems
2.1. Alphaviruses
2.2. Flaviviruses
2.3. Measles Viruses
2.4. Rhabdoviruses
3. Self-Replicating RNA Virus-Based Vaccines
3.1. Vaccines against Infectious Diseases
3.2. Vaccines against Cancer
3.3. Clinical Trials
4. Conclusions
Conflicts of Interest
Abbreviations
MDPI | Multidisciplinary Digital Publishing Institute |
DOAJ | Directory of open access journals |
CEA | Carcinoembryonic antigen |
CMV | Cytomegalovirus |
CRPC | Castration-resistant metastatic prostate cancer |
CRT | Calreticulin |
CTL | Cytotoxic T-lymphocyte |
DC | Dendritic cell |
EGFP | Enhanced green fluorescent protein |
EGFR | Epidermal growth factor receptor |
GFP | Green fluorescent protein |
GM-CSF | Granylocyte macrophage colony-stimulating factor |
GoI | Gene of interest |
HA | Hemagglutinin |
HBV | Hepatitis B virus |
HCC | Hepatocellular carcinoma |
HPV | zhuman papilloma virus |
IF3 | Initiation factor 3 |
IFN | Interferon |
IL | Interleukin |
ISG | Interferon-stimulated gene |
MERS-CoV | Middle East respiratory syndrome coronavirus |
MHC | Major histocompatibility complex |
miRNA | Micro RNA |
MLN | Mediastinal lymph nodes |
MV | Measles virus |
NIS | Sodium iodide symporter |
NP | Nucleoprotein |
PDAC | Pancreatic ductal adenocarcinoma |
PSMA | Prostate-specific membrane antigen |
PSCA | Prostate stem cell antigen |
RABV | Rabies virus; |
RSV | Respiratory syndrome virus |
SARS-CoV | Severe acute respiratory syndrome coronavirus |
SFV | Semliki Forest virus |
SEB | Staphylococcus enterotoxin B |
SIN | Sindbis virus |
ssRNA | Single-stranded RNA |
STEAP | Six-transmembrane epithelial antigen of the prostate |
TAA | Tumor-associated antigen |
TRAMP | Transgene adenocarcinoma of the mouse prostate |
TRP | Tyrosine-related protein |
Tyr | Tyrosinase |
VEE | Venezuelan equine encephalitis virus |
VEGFR | Vascular endothelial growth factor receptor |
VLPs | Virus-like particles |
VSV | Vesicular stomatitis virus |
WHV | Woodchuck hepatitis virus |
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Virus | Target | Vector | Immunization | Response | Reference |
---|---|---|---|---|---|
Influenza | NP | SFV VLPs | mouse | systemic NP immune response | [35] |
HA | VEE VLPs | chicken | protection against influenza virus | [36] | |
HA | VEE VLPs | swine | protection against influenza virus | [37] | |
HA | VEE VLPs | swine | protection against influenza virus | [38] | |
HA | rMV | mouse | neutralizing Abs | [39] | |
cHA | VSV | mouse | protection against influenza virus | [40] | |
HIV | Gag | Kunjin VLPs | mouse | protection against HIV | [41] |
Env | SFV VLPs | mouse | neutralizing Abs, humoral response | [42] | |
gp41 | SFV-VLPs | mouse | generation of mAbs | [43] | |
Env | SFV DNA | mouse | T cell and IgG immune responses | [44] | |
SIV | Gag-Pol | Kunjin VLPs | macaques | protection against SIV | [45] |
Env | VSV VLPs | macaques | neutralizing Abs | [46] | |
Gag-Env | VSV VLPs | macaques | protection against SIV | [47] | |
Gag-Env | RABV VLPs | macaques | protection against SIV | [48] | |
Ebola | GP | Kunjin VLPs | guinea pig | protection against Ebola | [49] |
GP | Kunjin VLPs | primate | protection against Ebola | [50] | |
GP | VSV VLPs | macaques | protection against Ebola | [51,52] | |
GP, NP | VEE VLPs | mouse | protection against Ebola | [53] | |
NP | VEE VLPs | mouse | protection against Ebola | [54] | |
Lassa | G | VSV VLPs | guinea pig | protection against Lassa | [55] |
G | VEE VLPs | guinea pig | protection against Lassa | [56] | |
SARS-CoV | G | VEE VLPs | mouse | protection against SARS-CoV | [57] |
MERS-CoV | G | MV | mouse | protection against SARS-CoV | [58] |
RSV | F | MV | rat | protection against RSV | [39] |
F | VEE LNPs | mouse | protection against RSV | [59] | |
F | VEE VLPs | primate | protection against RSV | [60] | |
MPV | F | VEE VLPs | primate | protection against MPV | [60] |
Dengue | DV2-HBsAg | MV | mouse | neutralizing Abs | [61] |
DV2 | MV | mouse | protection against dengue virus | [62] | |
prME-E85 | VEE VLPs | macaques | protection against dengue virus | [63] | |
prME-E85 | VEE VLPs | mouse | protection against dengue virus | [64] | |
HBV | MHB | SFV-VSV G | mouse | protection against HBV | [65] |
DV2-HBsAg | MV | mouse | protection against HBV | [62] | |
HBsAg | MV | macaques | protection against HBV | [66] | |
CMV | gB-pp65/IE1 | VEE VLPs | human | neutralizing Abs | [67] |
Agent | Target | Vector | Immunization | Response | Reference |
---|---|---|---|---|---|
P. falciparum | Ag Pf332 | SFV VLPs/RNA | mouse | immunological memory | [68] |
M. tuberculosis | Ag 85A | SIN DNA | mouse | protection against M. tuberculosis | [69] |
C. botulinum | BoNTA-Hc | SFV DNA | mouse | Ab and lymphoproliferative response | [70] |
B. abortus | IF3 | SFV VLPs | mouse | protection against Brucella | [71] |
B. antracis | PA | SIN VLPs | mouse | protection against B. antracis | [72] |
Malaria | CS | SIN VLPs | mouse | protection against malaria | [73] |
L. monocytogenes | OVA | VSV-GP | mouse | protection against Listeria | [74] |
Prion | PRNP | SFV VLPs | mouse | monoclonal Abs | [75] |
Staphylococcus | SEB | VEE VLPs | mouse | protection against enterotoxin | [76] |
Cancer | Target | Vector | Response | Reference |
---|---|---|---|---|
Brain | GFP, SLAM, EGFR | MV | replication in/lysis of cancer cells | [79] |
Endostatin | SFV VLPs | tumor inhibition | [89] | |
miR-124 | SFV-miR-124 | prolonged survival | [90] | |
IL-12 | SFV-IL-12 | prolonged survival | [91,92,93] | |
Breast | CEA | MV | tumor growth delay, better survival | [83] |
Neu | SIN DNA | immune responses, tumor protection | [94] | |
Neu | VEE VLPs + DCs | tumor regression by transduced DCs | [95] | |
VEGFR-2 | SFV VLPs | tumor inhibition | [96] | |
Cervical | HPV E6, 7 | SFV VLPs | tumor eradication | [97,98] |
HPV E7 | VEE VLPs | eradication of existing tumors | [99] | |
HPV E7 Epitope | Kunjin VLPs/RNA/DNA | tumor protection in mice | [88] | |
Colon | GM-CSF | Kunjin VLPs | regression of tumors and metastasis | [87] |
VEGFR-2 | SFV VLPs | reduced tumor and metastasis growth | [96] | |
LacZ | SFV RNA | tumor protection in mice | [100] | |
Lac Z | SIN VLPs | anti-tumor CD8+ T-cell immunity | [101] | |
IL-12 | SFV VLPs | tumor elimination | [102] | |
SFV | SFV VLPs | tumor growth inhibition | [103] | |
IL-18 | SFV VLPs | tumor regression in mice | [104] | |
Liver | IL-12 | SFV VLPs | anti-tumor responses in woodchucks | [105,106] |
Lung | HPV E6/E7 | SFV + Sun + Rad | tumor-free survival | [107] |
HPV E7-CRT | SIN VLPs | long-term anti-tumor effect | [108] | |
EGFP | SFV VLPs | apoptosis, tumor regression in mice | [109] | |
Melanoma | GM-CSF | Kunjin VLPs | tumor regression | [87] |
VEGF-2-IL-12 + Sur + β-hCG | SFV VLPs | tumor inhibition | [110] | |
TRP-2 | VEE VLPs | humoral and cellular immunity | [111] | |
Tyr | VEE VLPs | T-cell responses, tumor protection in mice | [112] | |
Ovarian | CEA, NIS | MV | superior dual therapy | [81] |
IL-12 | SIN VLPs | tumor targeting, eradication | [113] | |
IL-18 | SFV VLPs | therapeutic anti-tumor response | [91] | |
GM-CSF | SFV VLPs | tumor growth inhibition | [114] | |
Pancreatic | Matrix protein | VSV VLPs | killing of tumor cells in vitro and in vivo | [85] |
Prostate | CEA | MV | replication in/lysis of cancer cells | [79] |
PSMA | VEE VLPs | cellular and humoral immunity in mice | [115] | |
STEAP | VEE VLPs | CD8+ T-cell response, tumor growth delay | [116] | |
PSCA | DNA + VEE VLPs | long-term protective immune response | [117] | |
Sarcoma | PSA | VEE VLPs | PSA-cell clearance, tumor growth delay | [118] |
Skin | SFV | SFV VLPs | tumor growth inhibition | [103] |
P1A | SFV VLPs | strong CTL-response, tumor protection | [119] |
Viral Vector | Genome | Capacity | Special Features |
---|---|---|---|
Alphavirus | ssRNA | 6–8 kb | broad host range, high titer, cytoplasmic RNA, extreme transient expression, no chromosomal integration, choice of DNA, RNA replicon and particle delivery |
Flavivirus | ssRNA | 5 kb | broad host range, packaging system, choice of DNA, RNA replicon and particle delivery |
Measles virus | ssRNA | 5 kb | packaging cell line, measles virus strains for immunization, cytoplasmic RNA |
Rhabdovirus | ssRNA | 5 kb | reverse genetics systems, broad host range cytoplasmic RNA |
Adenovirus | dsDNA | >8 kb | broad host range, packaging cell line, nuclear translocation necessary, transient expression, potential integration |
AAV | ssDNA | <4 kb | multiple AAV serotypes for avoiding immune responses, nuclear translocation necessary, chromosomal integration |
Herpes simplex virus | dsDNA | 30–40 kb | large packaging capacity, nuclear translocation necessary, latent long-term transgene expression after integration |
Lentivirus | dsRNA | 8 kb | transduction of dividing and non-dividing cells, nuclear translocation necessary, chromosomal integration |
Retrovirus | dsRNA | 4 kb | transduction of only dividing cells, nuclear translocation necessary, chromosomal integration |
Vaccinia | dsDNA | 25 kb | large packaging capacity, nuclear translocation necessary |
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Lundstrom, K. Replicon RNA Viral Vectors as Vaccines. Vaccines 2016, 4, 39. https://doi.org/10.3390/vaccines4040039
Lundstrom K. Replicon RNA Viral Vectors as Vaccines. Vaccines. 2016; 4(4):39. https://doi.org/10.3390/vaccines4040039
Chicago/Turabian StyleLundstrom, Kenneth. 2016. "Replicon RNA Viral Vectors as Vaccines" Vaccines 4, no. 4: 39. https://doi.org/10.3390/vaccines4040039