Hepatitis C vaccine

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]

One effort has involved use of the hepatitis B core antigen.[3] 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.[4] Nevertheless, as of 2008 vaccines are still being tested.[5][6] Some efforts have entered Phase I/II human clinical trials.[7]

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.

Most vaccines work through inducing an antibody response that targets the outer surfaces of viruses, but the Hepatitis C virus is very variable. Since the antibody approach alone is not going to work, researchers are taking a different strategy, which 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.[8] Likely, vaccines following the first approved vaccine will address other genotypes by prevalence.

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 proteins 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.

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.

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.

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