Table 2.

Main prophylactic HCV vaccine candidates tested in chimpanzees

PROTOCOL	OUTCOME	Ref
Recombinant gpE1/gpE2 combined with oil/water adjuvents on months 0, 1 and 7 Challenge: 10–100 infectious doses of homologous HCV1 or heterologous HCV-H	21 vaccinated chimpanzees/24 controls (pooled results) 2/12 chronic infection after homologous challenge (pooled results) 1/9 chronic infection after heterologous challenge (pooled results) Strong humoral immune response 15/24 chronic infection in control animals (pooled results)	Choo Q.L. et al. and reviewed by Houghton M. et al. [88]
Recombinant DNA Plasmid: truncated E2, HCV 1a Challenge: 100 CID50 homologous monoclonal HCV	2 vaccinated chimpanzees/1 control 2/2 vaccinees: viral clearance High anti-E2 antibodies in one vaccinee E2-specific CD4+ response in the second	Forns X. et al. [90]
Recombinant DNA plasmid: core-E1–E2 + NS3-5, gHCV1b Booster: recombinant adenovirus NS3-5 Challenge: CID50 close but heterologous HCV1b	6 vaccinated chimpanzees/2 controls 2/6 vaccinees: viral clearance HCV specific antibody and T cell response Reduced peak viral load in all animals 1 sterilizing immunity: high anti-E2 and strong cellular response 1/2 control: viral clearance	Youn J.W. et al. [91]
Recombinant adenovirus NS3 -NS5B, HCV BK 1b Booster: plasmid DNA NS3-5B Challenge: heterologous H77 1a	5 vaccinated chimpanzees/5 controls 4/5 vaccinees: viral clearance after18 months Peripheral and intra-hepatic CD8+ T Ly cross-reacting with vaccine and challenge virus 3/5 control: viral clearance	Folgori A. et al. [92]
HCV-LP: core E1–E2, HCV1b Booster: HCV-LPs Challenge: 100 CID 50 homologous HCV-CG1b	4 vaccinated chimpanzees/4 controls 4/4 vaccinees: viral clearance after 12 months HCV specific IFN-γ+, IL-2+ CD4+, CD8+ T cell response in all vaccinees No neutralizing antibodies 1/4 control: viral clearance	Elmowalid G.A. et al. [104]
Recombinant DNA plasmids: Core E1–E2 and NS3, HCV 1b J4 Booster: MVA core E1–E2 and NS3 Challenge: heterologous HCV1bJ4	4 vaccinated chimpanzees/2 controls 1/4 vaccinees: viral clearance Reduction of HCV load in serum and liver Strong HCV CD4+ T cell response in all vaccinees Anti-E1 and anti-E2 specific antibodies in all vaccinees 3/4 chronic infections with high liver PD-1	Rollier C. et al. [105]
Recombinant vaccinia virus rVV: HCV 1b Core E1–E2-P7-NS2-NS3 Booster after 52 week: rVV Challenge: 24 CID50 homologous HCV Rechallenge: pool 20 CID50 of each 6 genotypes	4 vaccinated chimpanzees/2 controls 4/4 vaccinees: viral clearance after homologous Vigorous gamma-interferon enzyme-linked immunospot responses – moderate proliferative responses After multigenotype rechallenge: genotype 4 predominant during the early phase and 1a during the late phase; 2 negative after 60 weeks, 2 positive (low titer viremia)	Youn J.W. et al. [107]