Table 1.
Approaches in the Development of CCHFV Vaccines
| Vaccine type | CCHFV antigena | Mouse model | Doseb | Antibody response | T cell response | Challengec | Efficacy, % survival | Reference |
|---|---|---|---|---|---|---|---|---|
| Recombinant protein | Gc-e ectodomain (adjuvanted) Gn ectodomain (adjuvanted) Gc-eΔ ectodomain (adjuvanted) |
STAT-1−/− STAT-1−/− STAT-1−/− |
1.4 μg (i.p.) day 0 and 21 15 μg (i.p.) day 0 and 21 7.5 μg (i.p.) day 0 and 21 |
Yesd Yesd Yesd |
NT NT NT |
100 pfu CCHFV IbAr 10200 strain (s.c.) day 42 100 pfu CCHFV IbAr 10200 strain (s.c.) day 42 100 pfu CCHFV IbAr 10200 strain (s.c.) day 42 |
0% 0% 0% |
98 98 98 |
| Transgenic plants | Gn and Gc (Iranian strain) | BALB/c BALB/c BALB/c BALB/c BALB/c |
Fed leaves 10 μg 5 × (1-week intervals) Fed roots 10 μg 5 × (1-week intervals) Fed leaves 10 μg 4 × (1-week intervals) and injected 5 μg Gn/Gc Fed roots 10 μg 4 × (1-week intervals) and injected 5 μg Gn/Gc Bulgarian vaccine, injected four doses at 2-week intervals (s.c.) |
Yese Yese Yese Yese Yese |
NT NT NT NT NT |
NT NT NT NT NT |
NT NT NT NT NT |
99 99 99 99 99 |
| Virus-like replicon particles | GPC, L, and NP (IbAr 10200 L, NP, and Oman-1998 GPC ) GPC, L, and NP (IbAr 10200 L, NP, and Oman-1998 GPC) GPC, L, and NP (IbAr 10200 L, NP, and Oman-1998 GPC) Gn, Gc, and NP |
IFNAR−/− IFNAR−/− IFNAR−/− IFNAR−/− IFNAR−/− |
High dose (105 TCID50) (s.c.)f Low dose (103 TCID50) (s.c.)f 105 TCID50 (s.c.)f 105 TCID50 (s.c.)f 106 VLPs/mouse (i.p.) day 0, 28, and 49 |
Yese Yese Yese Yese Yesd |
NT NT NT NT Yes |
100 TCID50 recombinant CCHFV-IbAr 10200 (s.c.) day 32 100 TCID50 recombinant CCHFV-IbAr 10200 (s.c.) day 32 100 TCID50 CCHFV Oman-199723179 (s.c.) day 28 100 TCID50 CCHFV Turkey-200406546 (s.c.) day 28 400 FFU CCHFV strain IbAr 10200 (i.p.) day 91 |
100% 78% 100% 100% 40% |
109 109 110 110 100 |
| DNA | GPC Gn, Gc, and NP GPC GPC NP (Ank-2 strain) NP (Ank-2 strain) NP (Ank-2 strain) |
BALB/c BALB/c IFNAR−/− IFNAR−/− IS C57BL/6 BALB/c and IFNAR−/− BALB/c and IFNAR−/− BALB/c and IFNAR−/− |
10 μg (g.g.) day 0, 28, 56, and 84g 2.5 μg (g.g.) day 0, 28, 56, and 84h 50 μg (i.d.) day 0, 28, and 49 25 μg (i.m.) day 0, 21, and 42 25 μg (i.m.) day 0, 21, and 42 50 μg (i.m.) day 0 and 14 pV-N13 (50 μg) (i.m.) day 0 and 14 pV-N13 (40 μg) + pCD24 (10 μg) (i.m.) day 0 and 14 |
Yesd Yesd Yesd Yesd Yesd Yesi Yesi Yesi |
NT NT Yes NT NT Yes Yes Yes |
NT NT 400 FFU CCHFV strain IbAr 10200 (i.p.) day 91 100 pfu CCHFV strain IbAr 10200 (i.p.) day 70 100 pfu CCHFV strain IbAr 10200 (i.p.) day 70 1000 TCID50 of Ank-2 strain (i.p.) day 28 1000 TCID50 of Ank-2 strain (i.p.) day 28 1000 TCID50 of Ank-2 strain (i.p.) day 28 |
NT NT 100% 71% 60% 75% *50% 100% 100% |
113 113 100 77 77 90 89 89 |
| mRNA | NP | IFNα/βR−/− |
25 μg (i.m.)f 25 μg (i.m.) day 0, day 14 |
Yesi Yesi |
Yes Yes |
1000 TCID50 of Ank-2 strain (i.p.) day 42 1000 TCID50 of Ank-2 strain (i.p.) day 56 |
50% 100% |
104 104 |
| MVA vector Recombinant adenovirus type 5 Recombinant vesicular stomatitis virus Recombinant BoHV-4 Recombinant adenovirus type 5 Formalin inactivated vaccine |
GPC GPC NP NP NP (3010 strain) NP (3010 strain) NP NP GPC GPC NP (Ank-2 strain) NP (Ank-2 strain) Whole virus particle (Turkey-Kelkit06 strain) |
IFNα/βR−/− 129Sv/Ev IFNα/βR−/− 129Sv/Ev IFNα/βR-/ 129Sv/Ev IFNAR−/− IFNAR−/− STAT-1−/− STAT-1−/− BALB/c and IFNAR−/− BALB/c and IFNAR−/− IFNAR−/− IFNAR−/− IFNAR−/− |
107 pfu MVA-GP (i.m.) day 0 and 14 107 pfu MVA-GP (i.m.) day 0 and 14 107 pfu MVA-NP10200 (i.m.) day 0 and 14 107 pfu MVA-NP10200 (i.m.) day 0 and 14 107 pfu MVA-NP3010 (i.m.) day 0 and 14 107 pfu MVA-NP3010 (i.m.) day 0 and 14 1.25 × 107 ifu (i.m.)f 1.25 × 107 IFU (i.m.) day 0 and 108 IFU (i.n.) day 28 107 pfu (i.p.)f 107 pfu (i.p.) day 0 and 14 100 TCID50 (i.p.) day 0 and 14 100 TCID50 (i.p.) day 0 and 14 5 μg (i.p.) day 0, 21 and 42 20 μg (i.p.) day 0, 21 and 42 40 μg (i.p.) day 0, 21 and 42 |
Yese Yese Yese Yese Yese Yese NT Yese Yesd Yesd Yesi Yesi Yesd Yesd Yesd |
Yes Yes Yes Yes Yes Yes NT NT NT NT Yes Yes NT NT NT |
200 TCID50 CCHFV virus strain IbAr 10200 (i.d.) day 28 Not challenged 200 TCID50 CCHF virus strain IbAr 10200 (i.d.) day 28 Not challenged Not challenged Not challenged 50 TCID50 CCHFV strain IbAr 10200 (s.c.) day 28 50 TCID50 CCHFV strain IbAr 10200 (s.c.) day 56 50 pfu of CCHFV strain Turkey200406546 (i.p.) day 35 50 pfu of CCHFV strain Turkey200406546 (i.p.) day 35 1000 TCID50 of Ank-2 strain (i.p.) day 28 1000 TCID50 of Ank-2 strain (i.p.) day 28 1000 PPFU Turkey-Kelkit06 strain (i.p.) day 56 1000 PPFU Turkey-Kelkit06 strain (i.p.) day 56 1000 PPFU Turkey-Kelkit06 strain (i.p.) day 56 |
100% N/A 0% N/A N/A N/A 33% 78% 100% 100% 100% 75%j 100% 50%j 60% 80% 80% |
101 101 102 102 102 102 103 103 116 116 90 90 105 105 105 |
All vaccine candidates were based on IbAr 10200 strain unless otherwise stated.
Vaccine dose, timing, and route of inoculation, i.d.; i.p.; i.m.; i.n.; s.c.; g.g.
CCHFV challenge strain, dose, route, and timing.
Neutralizing antibodies in vitro.
Antibody ability to neutralize in vitro not assessed.
Single-dose administered.
Mice immunized with 10 μg of CCHF DNA vaccine.
Mice immunized with 2.5 μg of each of Rift Valley fever virus, CCHF, Hantaan virus and tick-borne encephalitis virus DNA vaccine.
Non-neutralizing antibodies in vitro.
Antibody passive and T cell adoptive transfer experiment.
BoHV-4, bovine herpesvirus type 4; Crimean–Congo hemorrhagic fever; CCHFV, Crimean–Congo hemorrhagic fever virus; ffu, focus-forming units; g.g., gene gun; GPC, glycoprotein precursor; i.d., intradermal; ifu, infectious units; i.m., intramuscular; i.n., intranasal; i.p., intraperitoneal; IFU, infectious units; IS, transiently suppressed type 1 interferon system; L, RNA-dependent RNA polymerase; mRNA, messenger RNA; MVA, modified Vaccinia Ankara virus; NP, nucleoprotein; NT, not tested; pfu, plaque-forming unit; PPFU, pseudo plaque-forming unit; s.c., subcutaneous.