Hepatitis C vaccine

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Hepatitis C vaccine
Vaccine description
Target Hepatitis C
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A hepatitis C vaccine, a vaccine capable of protecting against the hepatitis C virus (HCV), is not yet available. Although vaccines exist for hepatitis A and hepatitis B, development of an HCV 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 HCV virus is highly variable among strains and rapidly mutating, making an effective vaccine very difficult. [4]

Another strategy which is different from a conventional vaccine is to induce the T cell arm of the immune response using viral vectors, adenoviral vectors that contain large parts of the HCV genome itself, to induce a T cell immune response against HCV.[ 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.

VLP-based HCV 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 HCV, 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 HCV completely. [7]

Specific vaccines

As of 2020, Inovio Pharmaceuticals is developing a synthetic multi-antigen DNA vaccine covering 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] This vaccine is in Phase I clinical trial. [9]

The major histocompatibility complex class II-associated invariant chain (CD74)—fused with a viral vector to a conserved region of the HCV genome—has been tested as an adjuvant for an HCV vaccine in a cohort of 17 healthy human volunteers. This experimental vaccine was well-tolerated, and those who received the adjuvanted vaccine had stronger anti-HCV immune responses (enhanced magnitude, breadth and proliferative capacity of anti-HCV-specific T helper cells) compared with volunteers who received the vaccine that lacked this adjuvant. [10]

Related Research Articles

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Interferons are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten their anti-viral defenses.

<span class="mw-page-title-main">Hepatitis</span> Inflammation of the liver

Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pain, and diarrhea. Hepatitis is acute if it resolves within six months, and chronic if it lasts longer than six months. Acute hepatitis can resolve on its own, progress to chronic hepatitis, or (rarely) result in acute liver failure. Chronic hepatitis may progress to scarring of the liver (cirrhosis), liver failure, and liver cancer.

<span class="mw-page-title-main">DNA vaccine</span> Vaccine containing DNA

A DNA vaccine is a type of vaccine that transfects a specific antigen-coding DNA sequence into the cells of an organism as a mechanism to induce an immune response.

<span class="mw-page-title-main">HIV vaccine development</span> In-progress vaccinations that may prevent or treat HIV infections

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<span class="mw-page-title-main">Viral hepatitis</span> Liver inflammation from a viral infection

Viral hepatitis is liver inflammation due to a viral infection. It may present in acute form as a recent infection with relatively rapid onset, or in chronic form.

<span class="mw-page-title-main">Hepatitis C virus</span> Species of virus

The hepatitis C virus (HCV) is a small, enveloped, positive-sense single-stranded RNA virus of the family Flaviviridae. The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer and lymphomas in humans.

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Virus-like particles (VLPs) are molecules that closely resemble viruses, but are non-infectious because they contain no viral genetic material. They can be naturally occurring or synthesized through the individual expression of viral structural proteins, which can then self assemble into the virus-like structure. Combinations of structural capsid proteins from different viruses can be used to create recombinant VLPs. Both in-vivo assembly and in-vitro assembly have been successfully shown to form virus-like particles. VLPs derived from the Hepatitis B virus (HBV) and composed of the small HBV derived surface antigen (HBsAg) were described in 1968 from patient sera. VLPs have been produced from components of a wide variety of virus families including Parvoviridae, Retroviridae, Flaviviridae, Paramyxoviridae and bacteriophages. VLPs can be produced in multiple cell culture systems including bacteria, mammalian cell lines, insect cell lines, yeast and plant cells.

<span class="mw-page-title-main">CD74</span> Mammalian protein found in Homo sapiens

HLA class II histocompatibility antigen gamma chain also known as HLA-DR antigens-associated invariant chain or CD74, is a protein that in humans is encoded by the CD74 gene. The invariant chain is a polypeptide which plays a critical role in antigen presentation. It is involved in the formation and transport of MHC class II peptide complexes for the generation of CD4+ T cell responses. The cell surface form of the invariant chain is known as CD74. CD74 is a cell surface receptor for the cytokine macrophage migration inhibitory factor (MIF).

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References

  1. ↑ Randal J (June 1999). "Hepatitis C vaccine hampered by viral complexity, many technical restraints". Journal of the National Cancer Institute. 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". The Lancet. Infectious Diseases. 8 (6): 379–86. doi:10.1016/S1473-3099(08)70126-9. PMID   18501853.
  3. ↑ "Hepatitis C Questions and Answers for the Public". Centers for Disease Control and Prevention . 10 September 2019. Retrieved 20 April 2023.
  4. ↑ "Scripps Research Institute Scientists Achieve Most Detailed Picture Ever of Key Part of Hepatitis C Virus" (Press release). Scripps Research Institute. 28 November 2013. Retrieved 6 December 2013.
  5. ↑ "The hepatitis C virus". WHO. Archived from the original on 4 October 2013. Retrieved 1 October 2013.
  6. ↑ Torresi J (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. 1 2 Lombardi A, Mondelli MU (March 2019). "Hepatitis C: Is eradication possible?". Liver International. 39 (3): 416–426. doi: 10.1111/liv.14011 . PMID   30472772.
  8. ↑ Latimer B, Toporovski R, Yan J, Pankhong P, Morrow MP, Khan AS, 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): 2357–65. doi:10.4161/hv.29590. PMC   4896772 . PMID   25424943.
  9. ↑ Clinical trial number NCT02772003 for "DNA Vaccine Therapy in Treating Patients With Chronic Hepatitis C Virus Infection" at ClinicalTrials.gov
  10. ↑ Esposito I, Cicconi P, D'Alise AM, Brown A, Esposito M, Swadling L, et al. (June 2020). "MHC class II invariant chain-adjuvanted viral vectored vaccines enhances T cell responses in humans" (PDF). Science Translational Medicine. 12 (548): eaaz7715. doi:10.1126/scitranslmed.aaz7715. PMC   7610808 . PMID   32554708. S2CID   219722045.
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