Hepatitis C vaccine

A hepatitis C vaccine, a vaccine capable of protecting against hepatitis C, is not available. Although vaccines exist for hepatitis A and hepatitis B, development of a hepatitis C vaccine has presented challenges.[1] No vaccine is currently available, but several vaccines are currently under development.[2][3]

Most vaccines work through inducing an antibody response that targets the outer surfaces of viruses. However the Hepatitis C virus is highly variable among strains and rapidly mutating, making an effective vaccine very difficult.[4]

Another strategy which is different from conventional vaccine is to induce the T cell arm of the immune response using viral vectors, adenoviral vectors that contain large parts of the hepatitis C virus genome itself, to induce a T cell immune response against hepatitis C. Most of the work to develop a T cell vaccine has been done against a particular genotype. There are six different genotypes which reflect differences in the structure of the virus. The first approved vaccine will likely only target genotypes 1a and 1b, which account for over 60% of chronic hepatitis C virus infections worldwide.[5] Likely, vaccines following the first approved vaccine will address other genotypes by prevalence.

VLP (virus-like particles) based hepatitis C vaccines are also subject of intensive research.[6]

Since 2014, well-tolerated and extremely effective direct‐acting antiviral agents (DAAs) have been available which allows eradication of the disease in 8–12 weeks in most patients.[7] While this has changed treatment options drastically for patients with hepatitis C virus, it does not replace a vaccine that would prevent people from ever getting infected with the virus and will likely not be sufficient to eradicate the hepatitis C virus completely.[7]

Specific vaccines

Inovio Pharmaceuticals is developing a synthetic multi-antigen DNA vaccine covering hepatitis C virus (HCV) genotypes 1a and 1b and targeting the HCV antigens nonstructural protein 3 (NS3) and 4A (NS4A), as well as NS4B and NS5A proteins. Following immunization, rhesus macaques mounted strong HCV-specific T cell immune responses strikingly similar to those reported in patients who have cleared the virus on their own. The responses included strong HCV antigen-specific interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-2 (IL-2) induction, robust CD4 and CD8 T cell proliferation, and induction of polyfunctional T cells.[8] A Phase I clinical trial of the Inovio Pharmaceuticals vaccine is currently on-going [9]

References
  1. Randal, J. (2 June 1999). "Hepatitis C Vaccine Hampered by Viral Complexity, Many Technical Restraints". Journal of the National Cancer Institute. 91 (11): 906–908. doi:10.1093/jnci/91.11.906. PMID 10359539.
  2. Strickland, G Thomas; El-Kamary, Samer S; Klenerman, Paul; Nicosia, Alfredo (June 2008). "Hepatitis C vaccine: supply and demand". The Lancet Infectious Diseases. 8 (6): 379–386. doi:10.1016/S1473-3099(08)70126-9. PMID 18501853.
  3. "Hepatitis C Questions and Answers for the Public | CDC". 10 September 2019.
  4. Press Release (28 November 2013). "Scripps Research Institute Scientists Achieve Most Detailed Picture Ever of Key Part of Hepatitis C Virus". Scripps Research Institute. Retrieved 6 December 2013.
  5. "The hepatitis C virus". WHO. Archived from the original on 4 October 2013. Retrieved 1 October 2013.
  6. Torresi, Joseph (7 November 2017). "The Rationale for a Preventative HCV Virus-Like Particle (VLP) Vaccine". Frontiers in Microbiology. 8: 2163. doi:10.3389/fmicb.2017.02163. PMC 5674006. PMID 29163442.
  7. Lombardi, Andrea; Mondelli, Mario U.; ESCMID Study Group for Viral Hepatitis (ESGVH) (March 2019). "Hepatitis C: Is eradication possible?". Liver International. 39 (3): 416–426. doi:10.1111/liv.14011. ISSN 1478-3231. PMID 30472772.
  8. Latimer, Brian; Toporovski, Roberta; Yan, Jian; Pankhong, Panyupa; Morrow, Matthew P; Khan, Amir S; Sardesai, Niranjan Y; Welles, Seth L; Jacobson, Jeffrey M; Weiner, David B; Kutzler, Michele A (20 June 2014). "Strong HCV NS3/4a, NS4b, NS5a, NS5b-specific cellular immune responses induced in Rhesus macaques by a novel HCV genotype 1a/1b consensus DNA vaccine". Human Vaccines & Immunotherapeutics. 10 (8): 2357–2365. doi:10.4161/hv.29590. PMC 4896772. PMID 25424943.
  9. "DNA Vaccine Therapy in Treating Patients With Chronic Hepatitis C Virus Infection". ClinicalTrials.gov. Retrieved 10 May 2020.
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