By discovering how vital immune cells known as dendritic cells recognize dead and damaged cells, researchers think they may have found a new approach for next generation vaccines that “trick” cells into launching an immune response. Such vaccines would be more effective and result in fewer side-effects, they suggest.
Dendritic cells are unique immune cells that detect dead and damaged cells, digest them, and present them to other immune cells capable of recognizing foreign agents such as bacteria, viruses and parasites.
They are part of a family called antigen-presenting cells (APCs). But they are unique because they also send signals to other parts of the immune system, such resting T cells, to wake up and join the immune response.
Now for the first time, a large collaboration of immunologists, protein chemists and structural biologists, led by scientists at the Walter and Eliza Hall Institute in Parkville, Victoria, Australia, has identified how a protein on the surface of dendritic cells recognizes damage and trauma in cells that could signify infection.
They write about their work in a paper published online in the journal Immunity on 5 April.
Co-leader of the team, Dr Mireille Lahoud, who is now at the Centre for Immunology at the Burnet Institute in Melbourne, told the media, she and co-author Irina Caminschi, who is now also at the Burnet Institute had:
“… previously identified a protein called Clec9A (C-type lectin domain family 9A) that sits on the surface of specialised types of dendritic cells and responds to damaged and dying cells.”
In this latest study, Lahoud, Caminschi and colleagues found that Clec9A recognizes and binds to fibres of actin, a type of internal cell protein that is present in all cells of the body.
“Actin is only exposed when the cell membrane is damaged or destroyed, so it is an excellent way of finding cells that could harbour potentially dangerous infections and exposing them to the immune system,” explained Lahoud.
The researchers suggest that Clec9A could be the target of a new, more modern class of vaccine, one that is more effective and has fewer side effects.
The new vaccines could bind to Clec9A and con dendritic cells into reacting as though they had met a damaged cell, and trigger them into launching an immune response to the infectious agent chosen to be included in the vaccine.
Professor Ken Shortman of the Walter and Eliza Hall Institute is also a co-leader of the study team. He said you would need about 100 to 1,000 times less vaccine with such an approach:
“Traditional vaccine technology for generating immunity, such as using inactivated whole viruses or parasites for immune recognition, requires large amounts of vaccine in the hopes it will encounter the correct immune cells, and incorporates other substances (adjuvants) that are needed to signal to the immune system that something foreign is happening.”
Shortman said they envisage a new type of vaccine that would go straight to the right cell to trigger the immune response and would cause fewer side-effects because it would be more specific.
The team hope their findings will help develop or improve vaccines that presently are not as effective as we would like, such as those against diseases like malaria and HIV.
“There is also the possibility that the system could be used to develop therapeutic vaccines for treating diseases, such as some forms of cancer, as well as for preventing them,” said Lahoud.
Funds from the National Health and Medical Research Council of Australia, the Australian Research Council and the Victorian Government helped pay for the study.
Written by Catharine Paddock PhD