Hepatitis C, a viral infection instigated by the hepatitis C virus (HCV), predominantly impacts the liver, resulting in acute and chronic infections. Our company is dedicated to advancing the development of HCV vaccines and therapeutics, offering a range of services designed to expedite the journey from bench to bedside.
Introduction to Hepatitis C
Hepatitis C is a liver-focused viral infection triggered by the hepatitis C virus (HCV). This small, enveloped, positive-sense, single-stranded RNA virus is classified within the Flaviviridae family. The primary mode of transmission involves contact with infected blood, such as sharing needles for drug injections, needle-related accidents in healthcare environments, or receiving unscreened blood transfusions.
Acute hepatitis C infection commonly manifests with mild or asymptomatic symptoms, posing challenges for early detection. Nevertheless, in around 75-85% of instances, the virus persists, evolving into a chronic condition. Untreated chronic hepatitis C can result in substantial liver impairment, potentially culminating in conditions like cirrhosis and hepatocellular carcinoma. Globally, an estimated 80-160 million individuals grapple with chronic HCV infections, underscoring its substantial impact on global health.
Fig.1 Hepatitis C virus (HCV) life cycle. (Manns M. P., et al., 2017)
Vaccine Development for Hepatitis C
Subunit Vaccines
These vaccines utilize specific viral proteins, such as the E1 and E2 envelope glycoproteins, to stimulate an immune response. Examples include the development of recombinant HCV envelope proteins that have shown promise in preclinical studies.
Virus-Like Particles (VLPs)
VLPs mimic the structure of the virus, inducing an immune response without containing the viral genome. VLP-based vaccines have been tested, showing the potential to elicit neutralizing antibodies against HCV.
DNA and RNA-based Vaccines
DNA and RNA-based vaccines represent cutting-edge approaches that entail the direct delivery of genetic material encoding specific HCV antigens. By leveraging this innovative technology, these vaccines are designed to trigger robust immune responses.
Therapeutics Development for Hepatitis C
The introduction of direct-acting antivirals (DAAs) has revolutionized HCV therapeutics. These agents target specific viral proteins, leading to potent antiviral effects. Examples include:
- NS3/4A Protease Inhibitors: Drugs like grazoprevir and paritaprevir disrupt the viral replication process by inhibiting the NS3/4A protease.
- NS5B Polymerase Inhibitors: Sofosbuvir and velpatasvir are nucleotide analogs that inhibit the viral RNA polymerase, preventing viral replication.
- NS5A Inhibitors: Ledipasvir and daclatasvir target the NS5A protein, which plays a role in viral replication and assembly.
Table 1 Selected directly acting antiviral agents and host targeting agents in the pipeline. (Morozov V. A., et al., 2018)
|
Drugs name |
Target/active site |
Company |
Phase |
| NS3/4A protease inhibitors |
| Vaniprevir (MK-7009) |
Active site/macrocyclic |
Merck |
III |
| Voxilaprevir GS-9857 |
Active site |
Gilead |
III |
| Glecaprevir (ABT-493) |
Active site |
Abbvie |
III |
| IDX21437 |
Active site |
Idenix |
II |
| Sovaprevir (ACH-1625) |
Active site/macrocyclic? |
Achillion |
II |
| Nucleoside analog NS5B polymerase inhibitors (NI) |
| MK-3682 (formerly IDX20963) |
Active site |
Merck |
II |
| ACH-3422 |
Active site |
Achillion/Janssen |
II |
| Non- Nucleoside analog NS5B polymerase inhibitors (NNI) |
| Beclabuvir (BMS-791325) |
NNI site 1/Thumb 1 |
Bristol-Myers Squib |
III |
| Setrobuvir (ANA598) |
NNI site 4?/palm 1 |
Anadys/Roche |
II |
| NS5A inhibitors |
| BMS-824393 |
NS5A protein |
Bristol-Myers Squibb |
II |
| PPI-461 |
NS5A protein |
Presidio |
II |
| PPI-668 |
NS5A protein |
Presidio |
II |
| Pibrentasvir (ABT-530) |
NS5A protein |
Abbvie |
III |
| ACH-2928 |
NS5A protein |
Achillion |
I |
| Ruzasvir (MK-8408) |
NS5A protein |
Merck |
II |
| Host targeting agents |
| SCY-635 |
Cyclophilin inhibitor |
Scynexis |
II |
| Miravirsen |
miRNA122 antisense NA |
Santaris |
II |
| RG-101- |
miRNA122 antisense NA |
Regulus |
II |
| TT-0034 |
RNA interference with HCV |
Tacere Therapeutics |
II |
Our Services
The development of a Hepatitis C vaccine and effective therapies is a multifaceted process that requires a deep understanding of the virus, innovative scientific approaches, and robust preclinical research. Our team's deep understanding of HCV biology, combined with our expertise in vaccine and drug development, enables us to provide tailored solutions to our clients, accelerating their path to successful hepatitis C interventions.
Preclinical Research
- Pharmacodynamics Study Services
- Pharmacokinetics Study Services
- Drug Safety Evaluation Services
Disease Models
- Murine Models of HCV Entry and Infection
- HCV Infection Chimpanzee Models
- George Baker Virus B (GBV-B) Infection NHP Models
- Equine Hepacivirus (EqHV) Infection NHP Models
- Rodent Hepacivirus (RHV) Infection NHP Models
Our preclinical research services are designed to bridge the gap between discovery and clinical development. These services encompass:
- Viral Challenge Studies: Utilizing relevant animal models to assess the protective efficacy of vaccine candidates.
- Immunological Assessments: Evaluating the immune response induced by vaccine candidates, including the assessment of neutralizing antibody titers and T-cell responses.
- Pharmacokinetic and Pharmacodynamic Studies: Determining the absorption, distribution, metabolism, and excretion profiles of our therapeutic candidates.
If you are interested in our services, please feel free to contact us.
References
- Manns, Michael P., et al. "Hepatitis C virus infection." Nature reviews Disease primers 3.1 (2017): 1-19.
- Morozov, Vladimir Alexei, and Sylvie Lagaye. "Hepatitis C virus: Morphogenesis, infection, and therapy." World journal of hepatology 10.2 (2018): 186.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
