Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Genetic vaccine promising against chronic hepatitis C

07.06.2004


A potential vaccine candidate against chronic hepatitis C (HCV) infections is presented in a thesis from Karolinska Institutet. The new genetic vaccine can activate immune responses that are needed to clear HCV, a disease that today is difficult to treat effectively.



The hepatitis C virus (HCV) is a major cause of chronic liver disease worldwide. It is estimated that HCV affects approximately 170 million people around the world. Today, no vaccine is available to prevent or cure HCV infections. Antiviral therapy is used quite effectively, but in 60-80 per cent of the patients become chronic carriers of the virus in their liver. One feature of HCV infection is the high rate of viral persistence. The mechanism of viral persistence is largely unknown, although the high genetic variability is thought to play a key role.

In Lars Frelin’s thesis the HCV NS3 protein is studied in detail since it performs key functions in the viral life cycle. These are unwinding and strand separation of the viral RNA and proteolytic processing of the precursor polyprotein. To obtain the complete protease the NS4A co-factor was included in the NS3-based vaccines. NS4A has been shown to enhance the stability of NS3 and to target the NS3/4A complex to intracellular membranes. The latter is most likely of importance for the formation of the replication complex. Also, the NS3 region has a limited genetic variability and several studies have now demonstrated that NS3-specific CD4+ and CD8+ T-cell responses are crucial for the resolution of HCV infections. Thus, several factors suggest that the NS3 region should be well suited for vaccine development.


The results show that HCV NS3-based genetic vaccines effectively primed both humoral and cellular immune responses in mice. NS3/4A was shown to prime a Th1 CD4+ T-cell response. The inclusion of NS4A in NS3-based vaccines primed antibody, CD4+, and CD8+ T-cell responses that were superior to those primed by NS3-gene alone. Thus, NS4A enhanced the immunogenicity of NS3. The studies also show that enhancement of the immunogenicity was most probably a result of the higher expression levels of NS3 generated by the inclusion of NS4A. Further results show that the overall immunogenicity of NS3/4A could be further enhanced by codon optimization or by mRNA amplification using the Semliki forest virus (SFV) replicon. The NS3 protein expression levels were further improved by either codon optimization and mRNA amplification. Subsequently, both these modifications enhanced the NS3-specific immune responses. One concern in development of genetic vaccines is that the gene displays unwanted properties when expressed in vivo. Therefore, a new transgenic mouse expressing the HCV NS3/4Aprotein in the liver was generated. The protein expression was restricted to the liver to mimic the in vivo situation during a HCV infection. Protein expression was localized to the cytoplasm of the hepatocytes and displayed a similar staining pattern as seen in hepatocytes from HCV infected individuals. The intrahepatic protein expression did not cause overt liver damage, except for a slight enlargement of the liver. However, the NS3/4A-transgenic mice displayed less spontaneously appearing intrahepatic inflammatory foci, which are commonly found in laboratory mice. Thus, expression of NS3/4A-protein may affect the distribution of immune cells within the liver.

The present studies demonstrate that NS3/4A-based genetic vaccines effectively prime humoral and cellular immune responses. Intra-hepatic expression of NS3/4A did not cause any spontaneous liver disease or overt pathology suggesting that it safely can be used in genetic vaccines. Thus, the NS3/4A gene can safely activate immune responses that are similar to those found in humans who can clear HCV. The NS3/4A should therefore be a potential vaccine candidate against chronic HCV infections.

Ulla Bredberg-Radén | alfa

More articles from Health and Medicine:

nachricht One gene closer to regenerative therapy for muscular disorders
01.06.2017 | Cincinnati Children's Hospital Medical Center

nachricht The gut microbiota plays a key role in treatment with classic diabetes medication
01.06.2017 | University of Gothenburg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Individualized fiber components for the world market

23.06.2017 | Physics and Astronomy

How brains surrender to sleep

23.06.2017 | Life Sciences

Can we see monkeys from space? Emerging technologies to map biodiversity

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>