Table 1.
Summary of HCV vaccine candidates based on E1/E2 glycoproteins in preclinical or clinical trials
| Vaccine / HCV genotype | Target | Cross-genotype neutralization activity using HCVpp and/or HCVcc | Immunized species | Refs |
|---|---|---|---|---|
| rE2(Δ123) and rE2(Δ123A7) / HCV 1a (H77c) | E2 | 1a (H77), 2a (J6), 3a (S52), 5a (SA13) | Guinea pigs | [31] |
| rHCV E1/E2 with admixed sulfated S-lactosylarchaeol (SLA) archaeosome formulation as adjuvant / HCV 1a (H77) | E1E2 | N/A | C57BL/6 x BALB/c F1 mice | [32] |
| HCVp6-MAP. Six peptides (p6) in a multiple antigenic peptide (MAP) derived from conserved epitopes in E1 (1), E2 (2), NS4B (1), NS5A (1) and NS5B (1) / HCV 4a (ED43) | E1, E2, NS4b, NS5a, NS5b | 2a (JFH1) and a chimeric 2a/4a (ED43/JFH1) | BALB/c mice | [33] |
| DNA vaccine encoding sE1E2 into IMX313P (oligomers by fusion with the oligomerization domain of the C4b-binding protein) or sE1 and sE2 as separate immunogens / HCV 1b (HCV-N) | E1, E2, E1E2 | 1a (H77.20, UKN1A20.8), 1b (ukn1b5.23), 2a (ukn2a1.2, a2.4), 2b (UKN2B1.1, B2.8), 3a (UKN3A1.28, A1.9, A13.6), 4a (UKN4.11.1, 4.21.16), 5 (UKN5.14.4), 6 (UKN6.5.8, 6.5.340) | BALB/c mice | [34] |
| HCV-like particles bearing core, E1 and E2 from four genotypes / 1a (H77), 1b (BK), 2a (JFH1), and 3a | E1, E2, core | 1a (H77), 1b (BK), 2a (JFH1/J6, JFH1), 3a (HIC-109) |
BALB/c mice White Landrace pigs |
[35, 36] |
| Chimeric HBV/HCV virus‐like particles bearing three conservative linear epitopes from E1 and E2 and HVR1 mimotope / N/D | E1, E2 | 1a (JFH1/H77, H77C/JFH1), 1b (Hebei, J4/JFH1), 2a (JFH1/J6, JFH1) | BALB/c mice | [37] |
| rE2(Δ123) / HCV 1a (H77c) | E2 | 1a (H77c), 2a (J6), 3a (S52), 4a (ED43), 5a (SA13), 6a (EUHK2), 7a (QC69) | Albino Dunkin Hartley guinea pigs | [38] |
| rHCV E1/E2 with MF59C.1 as an adjuvant / HCV 1a | E1E2 | Genotype 1a/1b patients | Humans (Phase Ib) | [39] |
|
Chimeric HBV/HCV virus‐like particles bearing E1 or E2 / HCV 1a (JFH1/H77) |
E1, E2 | 1a (JFH1/H77; 7a), 1b (JFH1/J4; UKN5.23), 2a (JFH1 WT; UKN 2a1.2), 3 (JFH1/S52; UKN3A.1.28) | New Zealand rabbits | [40] |
| rHCV E1E2 / HCV 1a (HCV-1) | E1E2 | 1a (H77), 2a (J6), 3a (S52), 4a (ED43), 5a (SA13), 6a (HK6a) | Chimpanzees | [41] |
| HCV virus-like particles bearing E1E2 or E1 / HCV 1a (H77) | E1, E1E2 | 1a (H77), 1b (CG1b, CON1), 2a (JFH-1), 2b (UKN2B), 4c (UKN4) |
Macaques (Macaca fascicularis) Human CD46 ± IFNαβR-/- mice |
[42] |
| rHCV E1/E2 with MF59C.1 as an adjuvant (oil-in water emulsion) / HCV 1a | E1E2 | 1a (HCV-1, H77), 1b (UKN1B 12.6), 2a (J6), 3a (S52), 4a (UKN4.11.1), 5a (SA13) | C57BL/6J mice, macaques (Macaca mulatta), humans (Phase I, NCT00500747) | [43–46] |
| DNA vaccine expressing HCV Core, E1 and E2 / HCV 1b (CIGB-230) | E1, E2, core | N/A | Humans (Phase I) | [47–49] |
| HCV virus‐like particles bearing core, E1, and E2 with AS01B as an adjuvant (a combination of monophosphoryl lipid A and QS21 saponin) / HCV 1b (CG1b) | E1, E2, core | N/A | Chimpanzees (Pan Troglodytes) | [50] |
| rHCV E1 with aluminum hydroxide as an adjuvant / HCV 1b | E1 | N/A | Humans (Phase I) | [51] |
| DNA vaccine expressing HCV E2 / HCV 1a | E2 | N/A | Chimpanzees (Pan Troglodytes) | [52] |
Δ123: E2‐receptor‐binding domain lacking hypervariable region (HVR) 1 and 2, and the intergenotypic variable region (igVR) (384-408) or replaced with glutathione disulfide linkers (461-485 and570-580); Δ123A7: a disulfide-minimized version that contains seven cysteine to alanine mutations (A7: C452A, C486A, C569A, C581A, C585A, C597A, C652A); HCVcc: cell-cultured viruses; HCVpp: HCV pseudoparticles; N/A: Cross-reactive neutralizing antibodies not evaluated; N/D: Origin not indicated