Prophylactic and Therapeutic Vaccination against Hepatitis C Virus (HCV): Developments and Future Perspectives
Abstract
:1. Introduction
2. Genetic Diversity of HCV
3. HCV Kinetics During Primary and Secondary Infections
4. Immune Correlates of Viral Clearance
5. Prophylactic Vaccines
Vaccine(Genotype sequence used)(Number of animals vaccinated) | Immunogenicity | Challenge Inoculum*Dose (CID50§) | Outcome | Ref. |
---|---|---|---|---|
Recombinant gpE1/gpE2 in Oil/water adjuvants(Genotype 1a)(N=21) | Induced antibodies to E1E2 | Genotype 1aHomologous10 to 100CID50 | Protects against infection or chronic infection5 protected from infection14 resolved infection2 developed persistent infection | [72,73] |
DNA vaccine expressing E2 protein(Genotype 1a)(N=2) | Induced antibody and T cell responses to E2. | Genotype 1aHomologous100CID50 | Modifies infection, protects from chronic infection2 resolved infection | [74] |
Recombinant gpE1/gpE2 in oil/water adjuvants(Genotype 1a)(N=1) | Induced antibodies and cellular responses to E1E2 | Genotype 1aHomologous100CID50 | Delayed/modified infection1 developed persistent infection | [76] |
DNA prime and protein boost (using C, gpE1, gpE2 and NS3)(Genotypes 1a (core, NS3) and 1b (core, E1E2, NS3))(N=2) | Induced specific T-cell responses and antibody to E1 and E2. | Genotype 1bHomologous25CID50 | Modifies infection, protects from chronic infection1 resolved infection1 developed persistent infection | [77] |
DNA prime and Recombinant Adenovirus expressing core, E1,E2 and NS3 to NS5B(Genotype 1b)(N=6) | Induced specific T-cell responses and anti-E2 antibody (neutralizing) | Genotype 1bHomologous100CID50 | Modifies infection, protects from chronic infection1 protected from infection1 resolved infection4 developed persistent infection | [78] |
DNA prime and Recombinant VV expressing NS3,NS5A,NS5B(Genotype 1a)(N=1) | Induced specific T-cell responses | Genotype 1aHomologous100CID50 | Modifies infection1 developed persistent infection | [25] |
DNA prime and Recombinant Adenovirus expressing NS3 to NS5B(Genotype 1b)(N=5) | Induced specific T-cell responses | Genotype 1aHeterologous100CID50 | Modifies infection, protects from chronic infection4 resolved infection1 developed persistent infection | [26] |
DNA prime and rMVA boost (using C, gpE1, gpE2 and NS3)(Genotype 1b)(N=4) | Induced specific T-cell responses and antibody to E1 and E2. | Genotype 1bHomologous25CID50 | Modifies infection, protects from chronic infection1 resolved infection3 developed persistent infection | [79] |
Recombinant VLPs containing C, E1 and E2(Genotype 1b)(N=4) | Induced specific T-cell responses. No detectable anti-E1E2 response. | Genotype 1bHomologous100CID50 | Modifies infection, protects from chronic infection4 resolved infection | [75] |
Recombinant VV core, E1, E2, p7, NS2 and NS3(Genotype 1b)(N=4) | Induced specific T-cell responses. Weak anti-E1E2 response. | Genotype 1bHomologous2.5 and 24CID50† | Modifies infection, protects from chronic infection4 resolved infection | [70] |
DNA prime and Recombinant Adenovirus expressing NS3,NS5A,NS5B(Genotype 1a)(N=2) | Induced specific T-cell responses | Genotype 1aHomologous100CID50 | Modifies infection or protects from chronic infection1 resolved infection1 developed persistent infection | [71] |
Vaccine(Genotype sequence used) | Patient HCV Genotype | Immunogenicity | Outcome | Ref. |
---|---|---|---|---|
Alum-adjuvanted recombinant gpE1 protein(Genotype 1b) | *Genotype 1a Genotype 1b | Antibody and T-cell responses in some healthy volunteers.Boosts humoral and cellular responses in a subset of patients | May ameliorate hepatitis | [109,115,116] |
Peptide vaccine targeting E1, E2, NS3 and NS5A.(Genotype 1b) | Genotype 1b | Boosted peptide-specific T-cell and antibody responses. | Decreased ALT levels and HCV RNA levels in a subset of patients. | [106] |
DNA vaccine (CIGB-230) expressing core, E1, E2 plus recombinant core protein(Genotype 1b) | Genotype 1b | Boosted neutralizing antibody responses and T-cell responses in patients. | May ameliorate hepatitis | [110] |
Synthetic peptide vaccine (core, NS3, NS4) IC41 with or without poly-L-arginine.Genotype 1 | Genotype 1Genotype 3Genotype 4 | Boosted T-cell responses in patients. | Transient decline (>1-log) in HCV serum RNA titers in a subset of patients. | [107] |
V-5 Immunitor – heat-inactivated HCV antigens from HCV-infected donors administered orally in tablet form. (Genotype not defined) | Genotype not defined | Not measured. | Decreased liver enzyme levels. May improve HCV-associated clinical symptoms. | [111] |
ICOMATRIX-adjuvanted recombinant core protein(Genotype 1a) | Healthy patients used. | Induced HCV-specific immune responses and CD+ T-cell responses in a subset of patients. | Clinical trial in healthy adults, no HCV infected patients tested. | [117,118,119] |
MVA expressing NS3, NS4 and NS5B proteins (Transgene TG4040). (Genotype 1b) | Genotype not defined | Boosted HCV-specific immune responses | Transient decrease in viral load in a subset of patients. | [108,120,121] |
6. Therapeutic Vaccines
7. Conclusions
Acknowledgments
References
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Major, M.E. Prophylactic and Therapeutic Vaccination against Hepatitis C Virus (HCV): Developments and Future Perspectives. Viruses 2009, 1, 144-165. https://doi.org/10.3390/v1020144
Major ME. Prophylactic and Therapeutic Vaccination against Hepatitis C Virus (HCV): Developments and Future Perspectives. Viruses. 2009; 1(2):144-165. https://doi.org/10.3390/v1020144
Chicago/Turabian StyleMajor, Marian E. 2009. "Prophylactic and Therapeutic Vaccination against Hepatitis C Virus (HCV): Developments and Future Perspectives" Viruses 1, no. 2: 144-165. https://doi.org/10.3390/v1020144