Flu Discovery To Help Thwart Next Pandemic

Dr Steve Turner and Laureate Professor Peter Doherty, University of Melbourne Department of Immunology and Microbiology, and colleagues from St. Jude Children's Research Hospital, Memphis, USA have now discovered the key elements in the virus that are important in the T-cell's response, paving the way for a new class of vaccine against the flu strains that will cause the next pandemic.

Their research is published in the latest Proceedings of the National Academy of Sciences.

The flu virus is a cunning beast, constantly changing to avoid our body's immune defences. Our current method of protecting ourselves against the flu is via vaccination. These vaccines rely on priming our antibodies (antibody-mediated response) to fight related strains of flu that are placed in groups called serotypes. That is, vaccinations are developed to help protect us against one particular serotype.

Flu viruses have serotype-specific protein fragments on their outside surface that our antibodies will recognise and attach themselves to. This provides the signal to the body's other defense personnel to attack the infected cells. Unfortunately, it is these protein fragments that evolve and change rapidly over time, eventually rendering any vaccine ineffective.

Pandemics occur when there are large and sudden changes in the protein fragments on the virus' surface. The most recognised recent pandemic was the 1918 Spanish Flu which killed 20 million people.

"If another pandemic arose, it is unlikely a vaccine will be available in time to effectively combat such as strain," says Turner.

T-cells respond to proteins originally found inside the flu virus. These proteins rarely mutate, unlike those that antibodies respond to on the surface of the virus.

Turner and his colleague's discovery of how the T-cells respond to the flu virus has opened the door to development of a vaccine based on a T-cell (cell-mediated response), or one designed to generate such a response. Such a vaccine is likely to remain effective over time due to the stable nature of the proteins the T-cells respond to.

There are two types of cells that work together to fight disease. Antigen Presenting Cells (APC) carry out the first wave of attack. They devour the virus, chop up all the proteins inside its structure and then present particular fragments of these proteins on its surface. These fragments activate the Killer T-cells, to go and kill the flu virus. A proportion of these Killer T-cells remain after the virus has been eliminated (termed memory T cells) and they are primed for attack should any future viral invasion occur.

Turner and colleagues discovered the mechanisms of the T-cell response through a process called Reverse Genetics. This process allowed the scientists to mutate specific areas of the proteins (epitopes) within the virus that the Killer T-cell recognises on the surface of the APC.

Turner and the team from St Judes are now investigating two ways to develop a vaccine.

"The overall aim is to try and change the epitopes to make them elicit a stronger T-cell response," says Turner.

"The two ways we are trying to do this are to mutate the epitopes themselves to possibly produce a better immune response. The second way is to engineer the epitopes that exist inside the virus so that they appear on the outside of the virus coat. This will hopefully produce a cell-mediated response against these epitopes and therefore against the virus," he says.