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A peer-reviewed article of this preprint also exists.
This version is not peer-reviewed
Vaccine design platforms | Strain name and types of antigen | Animal Models |
Doses and vaccination strategies | Spesific antibody response | Neutralizing antibody response | T cell immune response | CCHFV challenge |
Survival rate% | References |
---|---|---|---|---|---|---|---|---|---|
Inactivated vaccines | Whole CCHFV from mouse-brain | NE | Several thousand people took repeated vaccination | NE | Yes | NE | NE | NE | [142] |
Bulgarian V42/81 strain; CCHFV whole antigen from mouse brain | NE | One group received a single dose, while the second group received four doses. | Yes | Yes | Yes | NE | NE | [143,144] | |
Turkey-Kelkit06 strain; CCHFV whole antigen from cell culture (Vero-E6) | IFNAR-/- mice and BALB/c mice with transiently immune suppressed by mAb-5A3 | IFNAR-/- mice: Administered (IP), at doses 5 μg, 20 μg and 40 μg of inactivated vaccine, on days 0, 21 and 42. BALB/c mice: Administered (IP), at doses 5 μg, 10 μg and 20 μg of inactivated vaccine, on days 0, 14 and 27. |
Yes | Yes | Yes | Turkey-Kelkit06 strain; 1000FFU (IFNAR-/-) and 100FFU (Balb/C) |
80% protected (IFNAR-/-), 100% protected (Balb/C) | [121,145,146] | |
Subunit vaccines | IbAr10200 strain; CCHFV Gn and Gc ectodomain | STAT1 knockout mice | Administered (IP), at doses 1.4 μg, 7.5 μg and 15 μg of Gn and Gc, on days 0 and 21 |
NE | Yes | NE | IbAr10200 strain; 100PFU | Not protected | [147] |
IbAr10200 strain; extracellular region of Gn (eGn), extracellular region of Gc with truncation of C terminal (eGc), neutralizing antibody region of Gc (NAB) | BALB/c mice | Administered (SC), at doses1 μg, 5 μg and 20 μg of surface display protein of G-GP with eGn, eGc, at weeks 0, 3, 6 and 9 |
Yes | Yes | Yes | NE | NE | [148] | |
Chinese Xinjiang strain HANM18; Gn and NP from CCHFV expressed in baculovirus expression system as rvAc-Gn, rvAc-NP and rvAc-Gn-NP | BALB/c mice | 107 PFU, on days 0, 14 and 28 |
Yes | NE | Yes | NE | NE | [149] | |
CCHFV Iranian strain; Gn and Gc expressed in transgenic tobacco leaves | BALB/c mice | Feeding (leaves), at dose 10 μg of Gc/Gn, at weeks 0, 1, 2 and 3 Feeding (roots), at dose 10 μg of Gc/Gn, at weeks 0, 1, 2, 3 |
Yes | NE | NE | NE | NE | [151] | |
DNA vaccines | IbAr10200 strain; GPC | BALB/c mice | Administered (gene gun), at dose 2.5 μg of the vaccine from each CCHFV+ RVFV + HTNV+ TBEV as total 10 μg, alone or combined, at weeks 0, 4 and 8 |
NE | Yes | NE | NE | NE | [154] |
IbAr10200 strain; Ubiquitin linked version of Gn, Gc and NP | IFNAR-/- mice | Administered (ID), at dose 15 μg of the vaccine three times with 4 weeks interval between 1st and 2nd dose and three weeks interval between 2nd and 3rd dose | Yes | Yes | Yes | IbAr10200 strain; 400FFU | 100% protected | [116] | |
IbAr10200 strain; GPC | IFNAR-/- mice and C57BL/6 mice with transiently immune suppressed by mAb-5A3 |
Administered (IM), at dose 25 μg of GPC, at weeks 0, 3 and 6 |
Yes | Yes | NE | IbAr10200 strain; 100PFU | Protective efficacy 71,4% for IFNAR-/- mice and 60% for transiently immune suppressed mice | [155] | |
IbAr 10200 strain; GPC from | C57BL/6 mice with transiently immune suppressed by mAb-5A3 | Administered (IM), at dose 50 μg of GPC, at weeks 0, 3 and 6 |
Yes | NE | Yes | IbAr10200 and Afg09-2990 strains; 100PFU |
100% protected against IbAr10200, 80% protected against Afg09-2990 |
[156] | |
Ank-2 strain; NP with CD24 |
BALB/c for immunological responses and IFNAR-/- mice for challenge studies | Administered (IM), at dose 50 μg of pV-N13 and 40 μg of pV-N13 with 10 μg of CD24, on days 0 and 14 |
Yes | NE | Yes | Ank-2 strain; 1000 TCID50 |
100% protected | [157] | |
IbAr10200 strain; NP, N terminal Gn and C terminal Gc fused with LAMP1 to generate three candidate vaccines | Human MHC (HLA-A11/DR1) | Administered (IM), at dose 70 μg pVAX-LAMP1-NP, 70 μg pVAX-LAMP1-Gn, 70 μg pVAX-LAMP1-Gc, at weeks 0, 3 and 6 |
Yes | Yes | Yes | IbAr10200 strain; 100 TCID50 CCHFV tecVLPS |
Instead of measuring survival percentages, NanoLuc activities measured, NP had the lowest levels of NanoLuc activities in their liver, spleen, and kidney | [158] | |
Hoti strain; Ubiquitin fused with GPC and NP |
Cynomolgus macaque | Administered (IM), at dose1 mg of pNP + 1 mg of pGPC, on days 0, 21 and 42 |
Yes | Poor neutralization acitivity | Yes | Hoti strain; 1X105 TCID50 |
Survival percentage was not assessed due to the non-uniform lethality of CCHFV in this animal model | [159] | |
Viral like replicon particles (VRP) vaccines | IbAr10200 strain; S and L segment, Oman 98 strain; M segment |
IFNAR-/- mice | Administered (SC), at dose 105 TCID50 or 103 TCID50 of VRPs, single vaccination |
Yes | NE | NE | IbAr1020 strain; 100 TCID50 |
Low dose showed 77% protection and high dose showed 100% protection | [160] |
IbAr10200 strain; S and L segment, Oman 98 strain; M segment |
IFNAR-/- mice | Administered (SC), at dose 1 × 105 TCID50 VRPs, single vaccination |
Yes | NE | NE | Oman 97 strain and CCHFV-Turkey strain; 100 TCID50 |
100% protected | [161] | |
IbAr10200 strain; S and L segment, Oman 98 strain; M segment |
IFNAR-/- mice | Administered (SC), at dose 1 × 105 TCID50 VRPs, single vaccination |
NE | NE | NE | CCHFV-Turkey strain; 100 TCID50 |
After 14,7, and 3days following vaccination; 100% protected |
[162] | |
Hoti strain; Gn and Gc |
BALB/c mice | Administered (SC), at dose 106 particles, at weeks 0, 2 and 5 |
Yes | Yes | NE | NE | NE | [164] | |
SPU 187/90 strain; NP | NIH-III Heterozygous mice strain | Administered (IM), at dose 100 μg Sindbis replicon (expressing NP), on days 0, 21 and 42 Administered (IM), at dose 100 μg of Sindbis replicon (expressing NP) + 50 μg Poly (I:C), on days 0, 21 and 42 |
Yes | NE | Yes | NE | NE | [166] | |
Hoti strain; NP and GPC |
C57BL/6 mice with transiently immune suppressed by mAb-5A3 | Administered (IM), at dose 2.5 μg of NP, 2.5 μ GPC and 5 μg of NP+GPC, on days 0 and 28 |
Yes | Poor neutralization activity | Yes | UG3010; 100TCID50 | 100% protected for NP and NP+GPC, 40% protected for GPC |
[167] | |
mRNA vaccines | Ank-2 strain; NP |
C57BL/6 mice for immunogenicity and IFNAR-/- mice for challenge studies |
Administered (IM), at dose 25 μg of NP, at weeks 0 and 2 |
Yes | No | Yes | Ank-2 strain; 100LD50 |
Double dose immunized group showed 100% protection | [170] |
IbAr10200 strain; NP, Gn and Gc | IFNAR-/- mice | Administered (ID), at doses 10 μg of NP, 10 μg of Gn, 10 μg of Gc and 20 μg of NP+ Gn+ Gc, at weeks 0 and 3 |
Yes | Yes | Yes | IbAr10200 strain; 400FFU |
100% protected | [171] | |
Viral vector-based vaccines | IbAr10200 strain; GPC expressed in modified vaccinia virus Ankara | IFNAR-/- mice | Administered (IM), at dose 107 PFU, at weeks 0 and 2 |
Yes | NE | Yes | IbAr10200 strain; 200TCID50 |
100% protected | [174] |
IbAr10200 strain; NP expressed in modified vaccinia virus Ankara | IFNAR-/- mice | Administered (IM), at dose 107 PFU, at weeks 0 and 2 |
Yes | NE% | Yes | IbAr10200 strain; 200TCID50 | Not protected | [175] | |
IbAr10200 strain; NP expressed in Adenovirus type 5 | IFNAR-/- mice | Administered (IM), 1.25x107 PFU for first dose at day 0, Administered (IN), 1x108 PFU for second dose at day 28 |
Yes | NE | NE | IbAr10200 strain; 1000LD50 | 78% protected | [177] | |
Ank-2 strain; NP expressed in Bovine Herpesvirus Type 4 (BoHV-4) |
BALB/c mice for serological assay and IFNAR-/- mice for challenge studies | Administered (IP), at dose 100 TCID50, at weeks 0 and 2 |
Yes | No | Yes | Ank-2 strain 100LD50 | 100% protected | [178] | |
IbAr10200 strain; GPC expressed in ChAdOx2 (Chimpanzee Adenovirus) | BALB/c mice for immunogenicity and IFNAR-/- mice for challenge studies | Administered (IM), at dose 5X107 infectious unit (IU), on days 0 and 14 |
Yes | Yes | Yes | IbAr10200 strain; 200FFU |
100% protected | [179] | |
IbAr10200 strain; GPC was expressed in Vesicular Stomatitis Virus expression system | STAT1 knock out mice | Administered (IP), at dose 107 PFU on days 0 and 21 |
Yes | Yes | NE | Turkey2004 strain; 50PFU |
100% protected | [180] |
CCHFV | Crimean-Congo hemorrhagic fever virus |
S | small |
M | medium |
L | large |
RdRp | RNA-dependent RNA polymerase |
NP | nucleoprotein |
GPC | glycoprotein precursor |
OTU | ovarian tumor |
IFN | interferon |
ISGs | interferon-stimulated genes |
IFNAR-/- | IFN1 deficient mice |
mAb | monoclonal antibody |
TLR | toll-like receptor |
PRRs | pattern recognition receptors |
PAMPs | pathogen-associated molecular patterns |
DIC | disseminated intravascular coagulation |
Nabs | neutralizing antibodies |
bsAbs | bispecific antibodies |
Stat1−/− | signal transducer and activator of transcription 1 |
IV | intravenous |
SC | subcutaneous |
NSM | nonstructural M protein |
MLD | mucin-like domain |
Al(OH)3 | aluminum hydroxide |
IS | immune-suppressed |
S2 | drosophila schneider 2 |
GEM-PA | enhancer matrix-protein anchor |
LAMP1 | lysosome-associated membrane protein 1 |
VRP | Virus like replicon |
VEEV | Venezuelan equine encephalitis virus |
WNV | West Nile virus |
LNP | lipid nanoparticle |
AdHu5 | adenovirus type 5 |
ChAdOx2 | chimpanzee adenovirus |
rVSV | recombinant vesicular stomatitis virus |
BoHV-4 | bovine herpesvirus type 4 |
ORF | open reading frame |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
Submitted:
28 June 2023
Posted:
28 June 2023
You are already at the latest version
A peer-reviewed article of this preprint also exists.
This version is not peer-reviewed
Submitted:
28 June 2023
Posted:
28 June 2023
You are already at the latest version
Vaccine design platforms | Strain name and types of antigen | Animal Models |
Doses and vaccination strategies | Spesific antibody response | Neutralizing antibody response | T cell immune response | CCHFV challenge |
Survival rate% | References |
---|---|---|---|---|---|---|---|---|---|
Inactivated vaccines | Whole CCHFV from mouse-brain | NE | Several thousand people took repeated vaccination | NE | Yes | NE | NE | NE | [142] |
Bulgarian V42/81 strain; CCHFV whole antigen from mouse brain | NE | One group received a single dose, while the second group received four doses. | Yes | Yes | Yes | NE | NE | [143,144] | |
Turkey-Kelkit06 strain; CCHFV whole antigen from cell culture (Vero-E6) | IFNAR-/- mice and BALB/c mice with transiently immune suppressed by mAb-5A3 | IFNAR-/- mice: Administered (IP), at doses 5 μg, 20 μg and 40 μg of inactivated vaccine, on days 0, 21 and 42. BALB/c mice: Administered (IP), at doses 5 μg, 10 μg and 20 μg of inactivated vaccine, on days 0, 14 and 27. |
Yes | Yes | Yes | Turkey-Kelkit06 strain; 1000FFU (IFNAR-/-) and 100FFU (Balb/C) |
80% protected (IFNAR-/-), 100% protected (Balb/C) | [121,145,146] | |
Subunit vaccines | IbAr10200 strain; CCHFV Gn and Gc ectodomain | STAT1 knockout mice | Administered (IP), at doses 1.4 μg, 7.5 μg and 15 μg of Gn and Gc, on days 0 and 21 |
NE | Yes | NE | IbAr10200 strain; 100PFU | Not protected | [147] |
IbAr10200 strain; extracellular region of Gn (eGn), extracellular region of Gc with truncation of C terminal (eGc), neutralizing antibody region of Gc (NAB) | BALB/c mice | Administered (SC), at doses1 μg, 5 μg and 20 μg of surface display protein of G-GP with eGn, eGc, at weeks 0, 3, 6 and 9 |
Yes | Yes | Yes | NE | NE | [148] | |
Chinese Xinjiang strain HANM18; Gn and NP from CCHFV expressed in baculovirus expression system as rvAc-Gn, rvAc-NP and rvAc-Gn-NP | BALB/c mice | 107 PFU, on days 0, 14 and 28 |
Yes | NE | Yes | NE | NE | [149] | |
CCHFV Iranian strain; Gn and Gc expressed in transgenic tobacco leaves | BALB/c mice | Feeding (leaves), at dose 10 μg of Gc/Gn, at weeks 0, 1, 2 and 3 Feeding (roots), at dose 10 μg of Gc/Gn, at weeks 0, 1, 2, 3 |
Yes | NE | NE | NE | NE | [151] | |
DNA vaccines | IbAr10200 strain; GPC | BALB/c mice | Administered (gene gun), at dose 2.5 μg of the vaccine from each CCHFV+ RVFV + HTNV+ TBEV as total 10 μg, alone or combined, at weeks 0, 4 and 8 |
NE | Yes | NE | NE | NE | [154] |
IbAr10200 strain; Ubiquitin linked version of Gn, Gc and NP | IFNAR-/- mice | Administered (ID), at dose 15 μg of the vaccine three times with 4 weeks interval between 1st and 2nd dose and three weeks interval between 2nd and 3rd dose | Yes | Yes | Yes | IbAr10200 strain; 400FFU | 100% protected | [116] | |
IbAr10200 strain; GPC | IFNAR-/- mice and C57BL/6 mice with transiently immune suppressed by mAb-5A3 |
Administered (IM), at dose 25 μg of GPC, at weeks 0, 3 and 6 |
Yes | Yes | NE | IbAr10200 strain; 100PFU | Protective efficacy 71,4% for IFNAR-/- mice and 60% for transiently immune suppressed mice | [155] | |
IbAr 10200 strain; GPC from | C57BL/6 mice with transiently immune suppressed by mAb-5A3 | Administered (IM), at dose 50 μg of GPC, at weeks 0, 3 and 6 |
Yes | NE | Yes | IbAr10200 and Afg09-2990 strains; 100PFU |
100% protected against IbAr10200, 80% protected against Afg09-2990 |
[156] | |
Ank-2 strain; NP with CD24 |
BALB/c for immunological responses and IFNAR-/- mice for challenge studies | Administered (IM), at dose 50 μg of pV-N13 and 40 μg of pV-N13 with 10 μg of CD24, on days 0 and 14 |
Yes | NE | Yes | Ank-2 strain; 1000 TCID50 |
100% protected | [157] | |
IbAr10200 strain; NP, N terminal Gn and C terminal Gc fused with LAMP1 to generate three candidate vaccines | Human MHC (HLA-A11/DR1) | Administered (IM), at dose 70 μg pVAX-LAMP1-NP, 70 μg pVAX-LAMP1-Gn, 70 μg pVAX-LAMP1-Gc, at weeks 0, 3 and 6 |
Yes | Yes | Yes | IbAr10200 strain; 100 TCID50 CCHFV tecVLPS |
Instead of measuring survival percentages, NanoLuc activities measured, NP had the lowest levels of NanoLuc activities in their liver, spleen, and kidney | [158] | |
Hoti strain; Ubiquitin fused with GPC and NP |
Cynomolgus macaque | Administered (IM), at dose1 mg of pNP + 1 mg of pGPC, on days 0, 21 and 42 |
Yes | Poor neutralization acitivity | Yes | Hoti strain; 1X105 TCID50 |
Survival percentage was not assessed due to the non-uniform lethality of CCHFV in this animal model | [159] | |
Viral like replicon particles (VRP) vaccines | IbAr10200 strain; S and L segment, Oman 98 strain; M segment |
IFNAR-/- mice | Administered (SC), at dose 105 TCID50 or 103 TCID50 of VRPs, single vaccination |
Yes | NE | NE | IbAr1020 strain; 100 TCID50 |
Low dose showed 77% protection and high dose showed 100% protection | [160] |
IbAr10200 strain; S and L segment, Oman 98 strain; M segment |
IFNAR-/- mice | Administered (SC), at dose 1 × 105 TCID50 VRPs, single vaccination |
Yes | NE | NE | Oman 97 strain and CCHFV-Turkey strain; 100 TCID50 |
100% protected | [161] | |
IbAr10200 strain; S and L segment, Oman 98 strain; M segment |
IFNAR-/- mice | Administered (SC), at dose 1 × 105 TCID50 VRPs, single vaccination |
NE | NE | NE | CCHFV-Turkey strain; 100 TCID50 |
After 14,7, and 3days following vaccination; 100% protected |
[162] | |
Hoti strain; Gn and Gc |
BALB/c mice | Administered (SC), at dose 106 particles, at weeks 0, 2 and 5 |
Yes | Yes | NE | NE | NE | [164] | |
SPU 187/90 strain; NP | NIH-III Heterozygous mice strain | Administered (IM), at dose 100 μg Sindbis replicon (expressing NP), on days 0, 21 and 42 Administered (IM), at dose 100 μg of Sindbis replicon (expressing NP) + 50 μg Poly (I:C), on days 0, 21 and 42 |
Yes | NE | Yes | NE | NE | [166] | |
Hoti strain; NP and GPC |
C57BL/6 mice with transiently immune suppressed by mAb-5A3 | Administered (IM), at dose 2.5 μg of NP, 2.5 μ GPC and 5 μg of NP+GPC, on days 0 and 28 |
Yes | Poor neutralization activity | Yes | UG3010; 100TCID50 | 100% protected for NP and NP+GPC, 40% protected for GPC |
[167] | |
mRNA vaccines | Ank-2 strain; NP |
C57BL/6 mice for immunogenicity and IFNAR-/- mice for challenge studies |
Administered (IM), at dose 25 μg of NP, at weeks 0 and 2 |
Yes | No | Yes | Ank-2 strain; 100LD50 |
Double dose immunized group showed 100% protection | [170] |
IbAr10200 strain; NP, Gn and Gc | IFNAR-/- mice | Administered (ID), at doses 10 μg of NP, 10 μg of Gn, 10 μg of Gc and 20 μg of NP+ Gn+ Gc, at weeks 0 and 3 |
Yes | Yes | Yes | IbAr10200 strain; 400FFU |
100% protected | [171] | |
Viral vector-based vaccines | IbAr10200 strain; GPC expressed in modified vaccinia virus Ankara | IFNAR-/- mice | Administered (IM), at dose 107 PFU, at weeks 0 and 2 |
Yes | NE | Yes | IbAr10200 strain; 200TCID50 |
100% protected | [174] |
IbAr10200 strain; NP expressed in modified vaccinia virus Ankara | IFNAR-/- mice | Administered (IM), at dose 107 PFU, at weeks 0 and 2 |
Yes | NE% | Yes | IbAr10200 strain; 200TCID50 | Not protected | [175] | |
IbAr10200 strain; NP expressed in Adenovirus type 5 | IFNAR-/- mice | Administered (IM), 1.25x107 PFU for first dose at day 0, Administered (IN), 1x108 PFU for second dose at day 28 |
Yes | NE | NE | IbAr10200 strain; 1000LD50 | 78% protected | [177] | |
Ank-2 strain; NP expressed in Bovine Herpesvirus Type 4 (BoHV-4) |
BALB/c mice for serological assay and IFNAR-/- mice for challenge studies | Administered (IP), at dose 100 TCID50, at weeks 0 and 2 |
Yes | No | Yes | Ank-2 strain 100LD50 | 100% protected | [178] | |
IbAr10200 strain; GPC expressed in ChAdOx2 (Chimpanzee Adenovirus) | BALB/c mice for immunogenicity and IFNAR-/- mice for challenge studies | Administered (IM), at dose 5X107 infectious unit (IU), on days 0 and 14 |
Yes | Yes | Yes | IbAr10200 strain; 200FFU |
100% protected | [179] | |
IbAr10200 strain; GPC was expressed in Vesicular Stomatitis Virus expression system | STAT1 knock out mice | Administered (IP), at dose 107 PFU on days 0 and 21 |
Yes | Yes | NE | Turkey2004 strain; 50PFU |
100% protected | [180] |
CCHFV | Crimean-Congo hemorrhagic fever virus |
S | small |
M | medium |
L | large |
RdRp | RNA-dependent RNA polymerase |
NP | nucleoprotein |
GPC | glycoprotein precursor |
OTU | ovarian tumor |
IFN | interferon |
ISGs | interferon-stimulated genes |
IFNAR-/- | IFN1 deficient mice |
mAb | monoclonal antibody |
TLR | toll-like receptor |
PRRs | pattern recognition receptors |
PAMPs | pathogen-associated molecular patterns |
DIC | disseminated intravascular coagulation |
Nabs | neutralizing antibodies |
bsAbs | bispecific antibodies |
Stat1−/− | signal transducer and activator of transcription 1 |
IV | intravenous |
SC | subcutaneous |
NSM | nonstructural M protein |
MLD | mucin-like domain |
Al(OH)3 | aluminum hydroxide |
IS | immune-suppressed |
S2 | drosophila schneider 2 |
GEM-PA | enhancer matrix-protein anchor |
LAMP1 | lysosome-associated membrane protein 1 |
VRP | Virus like replicon |
VEEV | Venezuelan equine encephalitis virus |
WNV | West Nile virus |
LNP | lipid nanoparticle |
AdHu5 | adenovirus type 5 |
ChAdOx2 | chimpanzee adenovirus |
rVSV | recombinant vesicular stomatitis virus |
BoHV-4 | bovine herpesvirus type 4 |
ORF | open reading frame |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
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