PROHEP

Augmentation of immune responses against hepatitis C virus by probiotic bacteria  

Consortium Leader: Professor Hannu Mykkänen, University of Kuopio, Department of Clinical Nutrition (www.uku.fi)

Other persons involved in the project:

ABSTRACT

Hepatitis C virus (HCV) infection is now recognised as the most common infection causing chronic liver disease in Europe. The number of HCV carriers in Europe alone is more than 5 million, and approximately 200 million worldwide. Chronic carriers of HCV are at risk of developing serious complications including cirrhosis, hepatocellular carcinoma and liver failure. The scale and cost of the global HCV pandemic, together with the limited efficacy, safety and accessibility of available therapies emphasizes the need for affordable approach for the management of this disease. Results from different laboratories, indicate that successful immunity against HCV involves potent Th1-type cellular responses. Notably, several studies indicate that certain probiotic bacteria possess ability to promote Th1-type T cell responses. These findings by us and others lead us to propose that Th1-polarizing probiotic bacteria, of clinically proven immunomodulatory capacity, will promote a sustainable and long term antiviral immune responses against hepatitis C infection with fewer and more tolerable side effects than associated with the current treatments. The overall aim of the project is to determine the impact of Th1-polarizing probiotic bacteria on HCV-specific T cell responses. Accordingly, the specific aims of the project are: 1) to find an optimal Th1-polarizing strain or a cocktail of strains by in vitro studies which compare a) the individual and synergistic effects of different probiotic strains on the phenotype and function of peripheral blood, colon and liver-derived dendritic cells (DCs) of HCV infected patients, and b) the ability of the probiotic-stimulated DCs to generate HCV antigen specific and non-specific antiviral T cell responses, 2) to characterize the immunomodulatory effects of probiotic bacteria, administered orally in escalating doses, on hepatic immune responses in vivo with an animal model, and 3) to determine, in a double-blind placebo-controlled proof of concept clinical trial, the strength of HCV-specific Th1 responses in patients with chronic HCV infection supplemented with the selected probiotic or probiotic cocktail. To achieve our ultimate goal, i.e. development of new dietary management strategies and functional food-based products for controlling HCV infection through the use of specific probiotic strains with validated Th1-polarizing effect, we have formed a collaborative group of international researchers representing the fields of expertise needed. We hope that this project will offer an opportunity to the Finnish food industries to develop their products in a new promising area of research (control of viral infection). The results of this project will facilitate further assessment of similar products in reducing the risk of immune related diseases and provide means for health promotion strategies especially among vulnerable groups in developing countries.

Key words:   hepatitis C virus, probiotics, immunomodulation, antiviral, developing countries