Hepatitis C vaccine

From Wikipedia, the free encyclopedia
Jump to: navigation, search

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]

Over the last decade numerous HCV vaccine approaches have been assessed in mice and primates. Only a small fraction of animal HCV vaccine studies have progressed to human trials. The majority of these trials have evaluated potential therapeutic vaccines in HCV-infected patients. A smaller number have assessed vaccines in healthy volunteers; either with the aim of developing a prophylactic HCV vaccine or as a bridge to evaluating vaccine in HCV-infected patients.

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, is 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 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.[citation needed]

Most of the work to develop a T cell vaccine has been done against a particular genotype.[citation needed] 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.

New HCV vaccine approaches, including peptide, recombinant protein, DNA and vector-based vaccines, have recently reached Phase I/II human clinical trials. Some of these technologies have generated robust antiviral immunity in healthy volunteers and infected patients. Novel future vaccine approaches include virus-like particle (VLP)-based vaccines that have been successfully employed for viral infections such as hepatitis B. Additional strategies include molecules that induce innate immune responses, with secondary effects on adaptive responses (such as TLR-9 ligands) that are either encoded within a vaccine construct or used as a vaccine adjuvant. The challenge now is to move forward into larger at-risk or infected populations to truly test efficacy.

Specific vaccines[edit]

One effort has involved use of the hepatitis B core antigen.[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.

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]

References[edit]

  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. ^ a b 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 3112461. 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.