Influenza Project

Core for Homeostatic Regulation

Influenza is a major life-threatening infectious disease in our society. Although the current vaccination method effectively reduces the risk of death, the following issues still remain.

1. What are the host factors that contribute to pathogenesis during the acute phase of infection?

Pathogenesis developed during infection varies among individuals. Several reports have suggested that dysregulation of immune responses might contribute to the pathogenesis. To understand the contribution of immune responses to pathogenesis, IMS has taken a systems biological approach. Gene expression profiles of subsets of tissue-invaded immune cells over time after infection are generated and analyzed.With this large dataset, IMS expects to identify new biomarkers, especially to predict the risk of death. The new biomarkers should enable us to prevent deaths from influenza by combining them with existing drugs.

2. Generating a next-generation vaccine against a broad range of influenza viruses.

Several groups have succeeded in isolating human and rodent antibodies that are broadly reactive with various influenza virus strains such as H1N1 and H5N1, findings that point to the feasibility of developing a universal vaccine. These antibodies mostly recognize the stem region of the Hemagglutinin (HA) protein, a region that is well-conserved at the amino acid sequence level. In the IMS influenza project, they are designing synthetic peptides to induce B cell antibody responses that can broadly neutralize influenza virus infections. Three teams from the research fields of immunology/biochemistry, computer science and structural biology are running this project, which aims to generate a next-generation vaccine for any upcoming pandemics resulting from antigenic shift and drift (Figure).

Figure: Crafting a universal vaccine for pandemic Influenza
A) Cross-reactivity of a "Universal" antibody. B) Numerous influenza peptides are designed and their affinities for "universal" antibody are predicted in silico. C) Selected peptides are subjected to biochemical binding analyses using the universal antibody. D) Potential peptides for the vaccine will be evaluated for their ability to generate "universal" antibody in vivo and to protect animals, and ultimately humans, from infection with various influenza virus strains.

Back to Projects