For a few years now infections with Hepatitis C virus can be efficiently treated and patients can be cured with modern medication. Nevertheless, researchers are looking for a vaccine against the virus, which has specialized itself on our liver, causing chronic infections and thereby still is the leading cause for liver transplantation. Reasons to search for a vaccine are obvious: The new treatment is very expensive and not available for all infected individuals. Furthermore, patients that have been cure are not protected from reinfection which often occurs in individuals at risk for acquisition of this pathogen. Researchers from TWINCORE recently published new approaches for a vaccine against the virus in the Journal of Hepatology.
Often, infections with HCV are not detected before they have become chronic and damage the liver. Therefore, a safe protection is only possible by a potent vaccination. Of course the search for a vaccine is not new. “The biggest problem of vaccine development is that the virus is very variable and many different variants are circulating worldwide, which constantly keep changing,“ Dr. Patrick Behrendt says, scientist in the Institute of Experimental Virology. Therefore the mission is to find parts of the virus surface that do not change and which ideally can be recognized by the immune system even decades later.
One of these stable – so-called conserved – parts of the virus surface is the binding site for the receptor CD81. The virus needs this part to enter the liver cells. It is the key to the infection of the cell and thus cannot be changed by the virus. A vaccine based on this part of the virus possibly leaves a strong, unique and long lasting impression on the immune system, so that the vaccinated body should be able to recognize numerous variants of HCV and fight them. So far the idea, but if this was so easy, a vaccine would already exist, says scientist Dr. Tanvi Khera. “The virus has very sophisticated protection mechanisms and seems to be aware of the susceptibility of this region. Structural analyses of the complex have shown us that this conserved structure is shielded by sugar structures and very variably parts of the virus like a protective coat.” This protective coat effectively prevents that those characteristic structures can be detected by immune cells or antibodies, both during an infection or when used as a vaccine. To improve the vaccination reaction against HCV, the researchers have removed parts of the protective coat by genetic modification of the virus. They presented this partly undressed complex to the immune system of mice and could detect a clear activation of the immune system – only for this variant of HCV though.
“These are good and important hints that guide us the way for the further search for a vaccine,“ says Dr. Dorothea Bankwitz, who will continue with the project in the institute. For instance the researchers are investigating the reason why it is so difficult to activate the immune system for the different variants of HCV. Or how they can trick the protective coat of the infection virus. “Unfortunately, HCV is extremely specialized on humans, so we can address many questions only by studying patient samples. In order to do that we have built a tight international research network to advance HCV vaccine research in the coming years.“
Contakt:
Dr. Patrick Behrendt, patrick.behrendt(at)twincore.de
Tel: +49 (0)511 220027-137
Prof. Dr. Thomas Pietschmann, thomas.pietschmann(at)twincore.de
Tel: +49 (0)511 220027-130
Publication:
Khera T, Behrendt P, Bankwitz D, Brown RJP, Todt D, Doepke M, Ghafoor Khan A, Schulze K, Law J, Logan M, Hockman D, Wong JAJ, Dold L, Gonzalez-Motos V, Spengler U, Viejo-Borbolla A, Stroh L, Krey T, Tarr AW, Steinmann E, Manns MP, Klein F, Guzman CA, Marcotrigiano J, Houghton M, Pietschmann T (2018) Functional and immunogenic characterization of diverse HCV glycoprotein E2 variants. J Hepatol (in press). (IF 14,911)