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]

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 fast mutated, making an effective vaccine very difficult.[3] 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.[3][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 HCV infections worldwide.[5] Likely, vaccines following the first approved vaccine will address other genotypes by prevalence.

Specific vaccines

One effort involved using hepatitis B core antigen modified to carry a hepatitis C protein.[6] 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.[7] Nevertheless, as of 2008 vaccines are still being tested.[8][9] Some efforts have entered Phase I/II human clinical trials.[10]

SynCon will test a new HCV vaccine in humans in 2013. SyCon's HCV vaccine can generate robust T-cell responses not only in the blood, but also in the liver—an organ known to suppress T-cell activity.

Inovio is developing a synthetic multi-antigen DNA vaccine covering hepatitis C virus (HCV) genotypes 1a and 1b and targeting the antigens NS3/4A, which includes HCV 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 NS3-specific interferon-γ (IFN-γ) induction, robust CD4 and CD8 T cell proliferation, and induction of polyfunctional T cells.

Under a 2011 development agreement, VGX International will fully fund IND-enabling, phase I, and phase II studies for their synthetic multi-antigen DNA vaccine covering hepatitis C virus (HCV) genotypes 1a and 1b vaccine.

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.[11][12]

Vaccines research

Development of a hepatitis C vaccine for horses most likely will bringing us closer to a vaccine against hepatitis C for humans. Scientists have only found HCV-like viruses in horses, rodents, and bats, without any of them actually being HCV as it appears in humans. The closest related virus is one resembling HCV in horses, while the viruses in rodents and bats are more distant relatives. Sequencing the genome of the HCV-like virus in horses will enable researchers to compare the HCV-like virus in horses with HCV in humans and other animals and this will help the scientists discover more about the relationship between the different viruses. An effective vaccine for horses will most probably lead to a vaccine for humans. Scientists can study the immune system's response to the virus in horses and study if vaccine candidates have any effect.

References

  1. ↑ Randal J (June 1999). "Hepatitis C vaccine hampered by viral complexity, many technical restraints". J. Natl. Cancer Inst. 91 (11): 906–8. doi:10.1093/jnci/91.11.906. PMID 10359539.
  2. ↑ Strickland GT, El-Kamary SS, Klenerman P, Nicosia A (June 2008). "Hepatitis C vaccine: supply and demand". Lancet Infect Dis. 8 (6): 379–86. doi:10.1016/S1473-3099(08)70126-9. PMID 18501853.
  3. 1 2 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.
  4. ↑ Kong, Leopold; Ward, Andrew; Wilson, Ian; Law, Mansun; Giang, Erick (2013). "Hepatitis C Virus E2 Envelope Glycoprotein Core Structure". Science. AAAS. 342 (6162): 1090–1094. doi:10.1126/science.1243876.
  5. ↑ "The hepatitis C virus". WHO. Retrieved 1 October 2013.
  6. ↑ Chen JY, Li F (December 2006). "Development of hepatitis C virus vaccine using hepatitis B core antigen as immuno-carrier". World J. Gastroenterol. 12 (48): 7774–8. PMID 17203519.
  7. ↑ Edell, Dean (2006). "Hepatitis C Vaccine Looks Promising". ABC7/KGO-TV. Retrieved 2006-07-04.
  8. ↑ Strickland GT, El-Kamary SS, Klenerman P, Nicosia A (June 2008). "Hepatitis C vaccine: supply and demand". Lancet Infect Dis. 8 (6): 379–86. doi:10.1016/S1473-3099(08)70126-9. PMID 18501853.
  9. ↑ HCV Vaccine Development
  10. ↑ 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 3112461Freely accessible. PMID 21604986.
  11. ↑ 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.
  12. ↑ Winter, Caroline (26 March 2014). "Adelaide researchers claim breakthrough in tackling HIV and hepatitis C with DNA vaccine". ABC abc.net.au. Retrieved 21 April 2014.
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