Copyright ©The Author(s) 2017.
World J Hepatol. Nov 28, 2017; 9(33): 1239-1252
Published online Nov 28, 2017. doi: 10.4254/wjh.v9.i33.1239
Table 1 Profile of direct-acting antiviral agents[4,37,40,42,44,48-78]
Direct-acting antiviral agentGeneric name (abbreviation)Code nameTrade nameActive against HCV genotype (based on clinical trial outcomes)Combination therapy
NS3/4A protease inhibitors (-previr)Telaprevir (TVR)VX-950Incivek/Incivo1TVR + IFN ± RBV
Boceprevir (BOC)SCH-503034 EBP-520Victrelis1BOC + IFN ± RBV
Faldaprevir (FDV)BI-201335-1FDV + Peg-IFN + RBV
Simeprevir (SIM)TMC-435Olysio1 and 4SIM + SOF ± RBV
Vaniprevir (VNV)MK-7009Vanihep1VNV + IFN ± RBV
Asunaprevir (ASV)BMS-650032Sunvepra1 and 4ASV + DCV
Paritaprevir (PTV)ABT-450Veruprevir1 and 4PTV+R+OBV+DAV ± RBV
Voxilaprevir (VOX)GS-9857-Pan-genotypic antiviral activityVOX + SOF + VPR
SovaprevirACH-1625-1Sovaprevir + ODV + RBV
Grazoprevir (GZP)MK-5172-1a, 1b, 4 and 6Zepatier (GZP + EBV)
Danoprevir (DNV)RG-7227-1 and 4DNV + PEG-IFN + RBV
Deldeprevir (DDV)ACH-2684 ACH-0142684-1DDV + ODV
Narlaprevir (NVR)SCH-900518Arlansa1NVR + R + PEG-IFN ± RBV
Vedroprevir (VDV)GS-9451-1VDV + LDV + SOF
Glecaprevir (GLE)ABT-493-Pan-genotypic antiviral activityGLE + PIB ± RBV
-GS-9256-1GS-9256 + PEG-IFN + RBV
GS-9256 + TGV + Peg-IFN ± RBV
NS5A replication complex inhibitors (-Asvir)Daclatasvir (DCV)BMS-790052Daklinza1, 2 and 3Sovodak (DCV + SOF) ± RBV
DCV + VX-135
Ledipasvir (LDV)GS-5885-1, 3, 4, 5 and 6Harvoni (LDV + SOF) ± RBV
LDV + SOF ± (VDV or Radalbuvir)
Ombitasvir (OBV)ABT-267-1 and 4Viekira Pak (OBV + PTV + R + DSV) ± RBV
Technivie (OBV + PTV + R)
Elbasvir (EBV)MK-8742-1a, 1b, 4 and 6Zepatier (EBV + GZP) ± RBV
Velpatasvir (VPR)GS-5816-Pan-genotypic antiviral activityEpclusa (VPR + SOF) ± RBV
Odalasvir (ODV)ACH-3102-1ODV + Sovaprevir + RBV
Ravidasvir (RVD)PPI-668-4RVD + SOF ± RBV
-JNJ-56914845-1GSK2336805 + PEG-IFN + RBV
GSK2336805GSK2336805 + VX-135 + SIM
SamatasvirIDX-18719 IDX-719-1, 2, 3 and 4Samatasvir + SIM + RBV
-BMS-824393-1BMS-824393 + PEG-IFN + RBV
Pibrentasvir (PIB)ABT-530-Pan-genotypic antiviral activityPIB + GLE ± RBV
Ruzasvir (RZR)MK-8408-Pan-genotypic antiviral activityRZR + UPR + GZP
Nucleoside NS5B polymerase inhibitorsSofosbuvir (SOF)PSI-7977;Sovaldi; SoforalPan-genotypic antiviral activitySOF + IFN ± RBV
(-Buvir)GS-7977Sovodak (DCV + SOF) ± RBV
Mericitabine (MCB)RG-7128-1 and 4MCB + PEG-IFN + RBV
RO5024048MCB + DNV
-VX-135-1VX-135 + GSK2336805 + SIM
ALS-2200VX-135 + TVR + RBV
VX-135 + DCV
VX-135 + RBV
VX-135 + SIM
ValopicitabineNM283-1Valopicitabine + Peg-IFN
Non-nucleoside NS5B polymerase inhibitors (-Buvir)Beclabuvir (BCV)BMS-791325-1BCV+ ASV+ DCV
Dasabuvir (DAV)ABT-333Exviera1DAV + OBV+ PTV + R ± RBV
LomibuvirVX-222-1VX-222 + TVR + RBV
VCH-222VX-222 + Filibuvir
FilibuvirPF-00868554,-1Filibuvir + Peg-IFN + RBV
PF-868554Filibuvir + VX-222
Setrobuvir (STV)ANA-598-1STV + IFN + RBV
RO-5466731STV + R + DNV + RBV ± MCB
Nesbuvir (NBV)HCV-796-1NBV +Peg-IFN + RBV
Tegobuvir (TGV)GS-9190-1TGV + GS-9256 +Peg-IFN ± RBV
Deleobuvir (DBV)BI-207127-1DBV + PEG-IFN + RBV
Uprifosbuvir (UPR)MK-3682-Pan-genotypic antiviral activityUPR + RZR
RadalbuvirGS-9669-1Radalbuvir + LDV + SOF
AL-335ALS-335-1AL-335 + ODV + SIM
Table 2 Vaccine candidates against hepatitis C virus in preclinical and clinical trials
Type of vaccineVaccine structure/adjuvantStage of developmentOutcomeApplicationDeveloperYearCurrent statusRef.
Recombinant protein vaccineRecombinant E1 or E2/MF597 chimpanzeesInduce strong humoral immune response; complete protection in 5 chimpanzeesProphylactic vaccineChiron/ Novartis1994Completed[101]
Recombinant E1 or E2/Alum4 ChimpanzeesInduce antigen-specific T-helper cytokines in either E1 orTherapeutic vaccineBPRC2011Published[102]
Recombinant E1/AlumPhase I 20 healthy volunteersE2-vaccinated animals; clear HCV infection in only E1-vaccinated animals (neutralizing antibodies) Induce strong cellular and humoral anti-E1 responsesTherapeutic vaccineFujirebio Europe2004Published[103]
Recombinant E1 and E2/MF59Phase I 60 healthy volunteersInduce humoral and cellular immune responsesProphylactic vaccineNovartis2010Completed[104]
Recombinant E1/AlumPhase I/II 20 healthy volunteers and 35 patients with chronic HCV infection/122 HCV-infected patientsInduce HCV specific humoral and cellular immune responses (Th1 type); no change in HCV viral loadTherapeutic vaccineInnogenetics/ GenImmune2003/2008Published[103,105,106]
HCV core protein/ISCOMATRIXPhase I/IIa 30 healthy volunteersInduce strong humoral immune responses in all except one patients; induce CD8+ T cell responses in 2 of 8 patients receiving the highest doseProphylactic vaccineCSL Ltd2009Published[107]
GI5005: Inactivated recombinant Saccharomyces cerevisiae expressing NS3-core fusion protein/ GI-5005 plus SOCPhase I/II 66 patients with chronic HCV infection/Improve SVRTherapeutic vaccineGlobeImmune2009/2010Completed[108,109]
Peptide-based vaccinePeptide from core protein (C35-C44)/ISA51Phase I 26 patients with chronic HCV infectionInduce peptide-specific cellular and humoral immune responses in 15 of 25 patients; decline HCV viral load in 2 of 25 patientsTherapeutic vaccineKarume University2009Published[110]
Four peptides from E1, E2, NS3 and NS5A/Freund’s adjuvantPhase I 12 nonresponder patients with chronic HCV infectionInduce peptide-specific cellular and humoral immune responses; decline HCV viral load in 3 patientsTherapeutic vaccineKarume University2007Published[111]
Autologous dendritic cell delivered six CD8+ T cell epitope peptides from core, NS3 and NS4BPhase I 6 nonresponder patients with chronic HCV infectionInduce transient T-cell responseTherapeutic vaccineBurnet Institute + others2010Completed[112]
IC41: Five peptides from core, NS3, and NS4/Poly-L-argininePhase I/II 128 volunteers/60 non-responders with chronic HCV infectionInduce HCV-specific T-cell responsesTherapeutic vaccineIntercell AG2006/2008Published[113,114]
IC41/Poly-L-arginine + imiquimodPhase I 54 healthy volunteersInduce significant T cell responses; low immunogenicity of topical imiquimodTherapeutic vaccineIntercell AG2010Published[115]
IC41 + imiquimodPhase II 50 HCV-infected patientsDecline viral load; induce T cell responsesTherapeutic vaccineIntercell AG2012Completed[116]
Virus-like particlesRecombinant HCV-like particles (HCV-LPs) containing core, E1, and E2/AS01B4 chimpanzeesInduce HCV-specific cellular immune responses; viral clearanceProphylactic vaccineNIH2007Published[117]
Recombinant baculovirus containing core, E1 and E2MiceInduce high titers of anti-E2 antibodies and strong HCV-specific cellular immune responses (CD8+ T and Th1 cells)Prophylactic vaccineNIH2001Published[118]
Bacterial-vectored vaccineAttenuated Salmonella typhimurium containing NS3 geneMiceInduce long-lasting T-cell responsesTherapeutic vaccineNIH2001Published[119]
Viral-vectored vaccineRecombinant adenoviral vectors and plasmid DNA expressing NS3-NS5B5 chimpanzeesInduce memory HCV-specific T cells; control of viremiaProphylactic vaccineNIH/Okairos2012Completed[120]
Multiple adenoviral vectors (Ad5, Ad6, Ad24, ChAd32 and ChAd33) expressing NS3-NS5B proteinsMice and rhesus macaqueInduce strong cellular immune responses; long-term maintenance of memory cellsProphylactic vaccineOkairos2006Published[121]
Recombinant vaccinia viruses (rVV) expressing core, E1, E2, P7, NS2 and NS34 chimpanzeesInduce cellular immune responses; reduce viral load; resolve HCV infectionProphylactic vaccineNYC Blood Center2008Published[122]
Recombinant adenoviral vectors (Ad6 and ChAd3) expressing NS3-NS5B proteinsPhase I 40 healthy volunteersInduce sustained HCV-specific T cell responsesProphylactic vaccineOkairos2012Completed[123]
Adenovirus vector (Ad6 and ChAd3) expressing NS3-NS5B proteinsPhase I 36 healthy volunteersHighly immunogenic; induce HCV specific T cell responsesProphylactic vaccineOkairos and Oxford University2009Published[124]
TG4040: MVA vector expressing NS3, NS4 and NS5B proteinsPhase I 15 patients with chronic HCV infectionDecline HCV viral load in 7 of 15 patients associated with T-cell responseTherapeutic vaccineTransgene2009Withdrawn[125]
MVA and ChAd3 vectors expressing NS3, NS4, NS5A and NS5B proteinsPhase I/II Healthy at risk population (68/472 IDU)July 28, 2018: Final data collection dateProphylactic vaccineNIAID2017Ongoing[126]
TG4040 + SOCPhase II 153 patients with chronic HCV infectionInduce HCV- and MVA-specific T-cell responses; develop anti-MVA antibodies; increase rate of early virologic responseTherapeutic vaccine-2014Published[127]
DNA vaccineRecombinant DNA plasmid encoding E22 chimpanzeesInduce humoral and cellular immune responses; resolve the infection; prevent progression to chronicityProphylactic vaccineNIAID/NIH2000Published[128]
Recombinant DNA plasmid and adenovirus vector expressing core, E1, E2 and NS3-58 chimpanzeesInduce HCV-specific T-cell and long-lasting E2-specific antibody responses; reduce viral loadProphylactic vaccineNIH2005Published[129]
Recombinant DNA plasmids and MVA vector expressing core, E1, E2 and NS36 chimpanzeesInduce HCV-specific immune responses; reduce viral load; early control of acute HCV infection; fail to impact on chronicityProphylactic vaccineTransgene2007Published[130]
CIGB-230: Plasmid expressing core/E1/E2 plus recombinant core proteinPhase I 15 non-responder patients with chronic HCV infectionInduce humoral and cellular immune responses; no viral clearanceTherapeutic vaccineUniversity of Montreal + others2009Published[131]
ChronVac-C: Plasmid expressing NS3 and NS4A delivered by in vivo electroporationPhase I/IIa 12 HCV-infected patientsDecline HCV viral load in 4 of 6 patients receiving the highest dose with corresponding HCV-specific T-cell response in 3 patientsTherapeutic vaccineTripep AB2009Recruiting[132]