New way to improve vaccines against cancer and infectious diseases

Research groups from Charité Universitätsmedizin Berlin and the University of Geneva have discovered a new way of improving vaccines against infectious diseases and for use in cancer therapies. Scientists have shown a basic new mechanism that stimulates the body's own alarm signals in case of viral infection to animate the immune system to maximum performance.

Viral infections activate so-called killer T cells. These form an important part of the body's defense. They can recognize and destroy cells that are infected with viruses or have degenerated into cancer cells. Thus, killer T cells would be an important mechanism in vaccines against HIV/AIDS, hepatitis C, malaria, and in cancer therapies. To date, there are no vaccines available for any of these diseases. Killer T cells are activated by dendritic cells. These coordinate the body's immune response.

The German-Swiss research group, surrounding Prof. Max Löhning from Charité and Prof. Daniel Pinschewer from University of Geneva, has now discovered a second mechanism that indicates how a viral infection stimulates killer T cells to maximum performance. Prof. Löhning explains: "The virus-infected, dying cells ring the alarm bells to the killer T cells themselves."

When viruses destroy infected cells, cell matter is released that is usually invisible to killer T cells. This matter includes so-called alarmins. The scientists have discovered that killer T cells recognize the alarmin interleukin-33. In case of cell death, the cells that form the framework of the spleen and lymph nodes and are in direct proximity to killer T cells, release this alarmin.

In experiments with mice, researchers determined that mice missing the interleukin-33 gene failed to generate large numbers of killer T cells upon viral infection. The few cells remaining were only barely active. Conversely, administering the relevant alarmin during vaccination led to a large increase in killer T cells. These new findings form an important basis for the development of effective vaccines against infectious diseases and for cancer therapies.