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 Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University

nachricht The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute

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: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>