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] The detailed structure of E2 envelope glycoprotein, believed to be the key protein the virus uses to invade liver cells, was elucidated by scientists at The Scripps Research Institute (TSRI) in November 2013. Due to the relatively conserved binding region of E2 to the CD81 receptor on the liver cells, this discovery is expected to pave the way to design a HCV vaccine which will stimulate antibody response with neutralizing effects on broad range of virus strains.[4][5] 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 HCV infections worldwide.[6] Likely, vaccines following the first approved vaccine will address other genotypes by prevalence.

VLP (virus-like particles) based HCV vaccines are also subject of intensive research.[7]

Specific vaccines

One effort involved using hepatitis B core antigen modified to carry a hepatitis C protein.[8] In a 2006 study, 60 patients received four different doses of an experimental hepatitis C vaccine. All the patients produced antibodies that the researchers believe could protect them from the virus.[9] Nevertheless, as of 2008, vaccines are still being tested.[10][11] Some efforts have entered Phase I/II human clinical trials.[12]

Inovio 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. Inovio has the intent to initiate a phase I/IIa clinical study in the fourth quarter of 2013. 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.[13]

In 2014, South Australian researchers have claimed to have had success treating hepatitis C using a new type of cutaneous DNA vaccine. Injecting directly into the skin, which has more white blood cells than muscle tissue, induces inflammation at the injection site and attracts more white blood cells. The vaccine was developed to treat patients with hepatitis C, but researchers speculate that it may be used as a preventative vaccine for hepatitis C and HIV within the next five years.[14][15]

References

  1. Randal, J. (1999). "Hepatitis C Vaccine Hampered by Viral Complexity, Many Technical Restraints". JNCI Journal of the National Cancer Institute. 91 (11): 906–908. doi:10.1093/jnci/91.11.906. ISSN 0027-8874. PMID 10359539.
  2. Strickland, G Thomas; El-Kamary, Samer S; Klenerman, Paul; Nicosia, Alfredo (2008). "Hepatitis C vaccine: supply and demand". The Lancet Infectious Diseases. 8 (6): 379–386. doi:10.1016/S1473-3099(08)70126-9. ISSN 1473-3099. PMID 18501853.
  3. https://www.cdc.gov/hepatitis/hcv/cfaq.htm#G1
  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. Kong, L.; Giang, E.; Nieusma, T.; Kadam, R. U.; Cogburn, K. E.; et al. (2013). "Hepatitis C Virus E2 Envelope Glycoprotein Core Structure". Science. 342 (6162): 1090–1094. Bibcode:2013Sci...342.1090K. doi:10.1126/science.1243876. ISSN 0036-8075. PMC 3954638. PMID 24288331.
  6. "The hepatitis C virus". WHO. Archived from the original on 4 October 2013. Retrieved 1 October 2013.
  7. "The Rationale for a Preventative HCV Virus-Like Particle (VLP) Vaccine". europepmc.org. 7 November 2017. Retrieved 26 December 2017.
  8. Chen, Jia-Yu; Li, Fan (28 December 2006). "Development of hepatitis C virus vaccine using hepatitis B core antigen as immuno-carrier". World Journal of Gastroenterology. 12 (48): 7774–7778. doi:10.3748/wjg.v12.i48.7774. ISSN 1007-9327. PMC 4087541. PMID 17203519.
  9. Edell, Dean (2006). "Hepatitis C Vaccine Looks Promising". ABC7/KGO-TV. Archived from the original on 5 October 2006. Retrieved 4 July 2006.
  10. Strickland, G. Thomas; El-Kamary, Samer S.; Klenerman, Paul; Nicosia, Alfredo (2008). "Hepatitis C vaccine: supply and demand". The Lancet Infectious Diseases. Elsevier BV. 8 (6): 379–386. doi:10.1016/s1473-3099(08)70126-9. PMID 18501853.
  11. "Initiative for Vaccine Research (IVR): Infectious diseases: HCV Vaccine Development". WHO. Archived from the original on 22 March 2006.
  12. Halliday, J.; Klenerman, P.; Barnes, E. (May 2011). "Vaccination for hepatitis C virus: closing in on an evasive target". Expert Rev Vaccines. 10 (5): 659–72. doi:10.1586/erv.11.55. PMC 3112461. PMID 21604986.
  13. Latimer, Brian; Toporovski, Roberta; Yan, Jian; Pankhong, Panyupa; Morrow, Matthew P; et al. (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. ISSN 2164-5515. PMC 4896772. PMID 25424943.
  14. Winter, Caroline (25 March 2014). "Adelaide researchers claim significant breakthrough in tackling HIV, hepatitis C - Radio interview transcript". PM Radio abc.net.au. Retrieved 21 April 2014.
  15. Winter, Caroline (26 March 2014). "Adelaide researchers claim breakthrough in tackling HIV and hepatitis C with DNA vaccine". ABC. Retrieved 21 April 2014.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.