New vaccines on the horizon
Despite the fact that vaccines have saved lives for over 200 years, modern vaccine research has only just begun to develop their potential. New knowledge opens new doors: one day, we might be able to inoculate ourselves against cancer, dementia and cardiovascular disease.
While increasingly refined vaccine candidates are being developed in the fight against the most serious infection diseases, pioneering scientists are directing the vaccine weapon at other targets, such as cancer.
Preventative vaccines against cancer-causing viruses have been successfully developed, including one against the HPV virus (the cause of cervical cancer), which is due for inclusion in Sweden´s public vaccination programme.
But most forms of cancer are not caused by viruses and must therefore be attacked by other means. Research is underway to develop therapeutic vaccines to be given after the establishment of the disease, and that make the immune defence attack the tumour itself. According to Rolf Kiessling, professor of experimental oncology at the Department of Oncology-Pathology, several hundred therapeutic cancer vaccines are being tested around the world. However, cancer vaccines have proved more difficult to develop than many first thought, and the big breakthrough will have to wait.
Bacteria and viruses carry molecules that are often totally foreign to the body and that the immune system has developed the ability to recognise; when it comes to the body´s own cells, on the other hand, the immune defence has developed several suppressor mechanisms to prevent them from being attacked, which is what occurs during autoimmune diseases.
"Tumour cells aren´t that different from the healthy cells in our bodies, and so the challenge is to get the immune defence to attack them without harming the healthy cells," says Professor Kiessling.
In their efforts to develop a cancer vaccine, researchers are using various creative methods to produce a kind of "benign autoimmune reaction" that specifically knocks out tumour cells but leaves healthy cells unharmed. One strategy for removing the immune defence´s tolerance of the tumour and to make it appear as "foreign" is to use an adjuvant containing bacterial DNA. Another is to try to find the tumour antigen that differs as much as possible from the body. A third is to combine vaccination with low doses of chemotherapy, which temporarily reduces the immune defence´s suppressor mechanisms.
Professor Kiessling himself is trying to develop vaccines for breast cancer and malignant melanoma, a severe type of skin cancer. The breast cancer vaccine is a DNA vaccine that contains an oncogene (a gene that causes cancer) expressed in breast cancer tumours. The malignant melanoma vaccine, on the other hand, contains dendritic cells from the patient combined with antigens from surgically removed cancer cells. When the dendritic cells are introduced back into the patient, they activate the immune defence against the cancer cells.
The research field has enjoyed something of an upsurge in recent years, says Professor Kiessling. One promising example is the attempt to develop a vaccine for prostate cancer.
"It´s related to the fact that the prostate is a clearly defined organ with a unique structure," explains Professor Kiessling. "Prostrate tumours contain cells not found anywhere else in the body and that are therefore suitable targets for a vaccine."
Text: Ola Danielsson. Published in Medicinsk Vetenskap nr 1 2010.
Combating cardiovascular disease with vaccines
Cardiovascular disease is the greatest health problem in Sweden today. Scientists have known that the immune defence is involved in the disease process since the 1980s, and attempts to produce a vaccine have now gained momentum.
That atherosclerosis was the result of an inflammatory process involving the immune defence was demonstrated in the early 1980s by Göran K Hansson, professor of experimental cardiovascular research at Karolinska Institutet. His results opened the way for the eventual development of a vaccine against the disease. However, it has only been in the past decade that the important role played by the immune defence in atherosclerosis has gained widespread acceptance, and several research groups are now trying to find possible means of treating cardiovascular disease with vaccines.
Professor Hansson and Professor Jan Nilsson in Malmö have together developed an antibody-based immunotherapy and a preventative vaccine against atherosclerosis, both of which are now being tested on humans. The therapies, which have previously been proved efficacious in mice, target components of LDL, the "bad" cholesterol, which infiltrates the blood vessels and starts the atherosclerosis process.
In parallel with this is the development of second generation vaccines that will provide even more specific immune defence. The researchers have discovered that this is more easily achieved when the antigen is introduced through the mucus membranes rather than through the blood, and have therefore developed a vaccine in the form of a nasal spray, which has recently been shown to produce the desired results in mice.
"The results look very promising and we hope to be able to take the development of this `anti-heart attack nasal spray´ further," says Professor Hansson.
Research is also underway at Karolinska Institutet to identify possible vaccine targets amongst other components (namely phospholipids) of the plaque that builds up in the blood vessels to cause atherosclerosis. Johan Frostegård, professor of medicine at the Department of Medicine in Huddinge has shown that high levels of a specific type of natural antibody in the immune defence (anti-PC) is associated with a lower risk of atherosclerosis, and low levels of anti-PC with a higher risk of consequences such as thrombi and myocardial infarction. The hypothesis is that these antibodies, which the group has shown to have an anti-inflammatory effect, react to the phosphocholine (PC) molecule in the plaque. Professor Frostegård notes that the advantage of these natural antibodies is that they are endogenous, which raises the possibility of stimulating an immune defence that already exists but that is inadequate.
"We´re developing new immunological treatments for atherosclerosis, either in the form of a vaccine that stimulates the immune defence to form PC antibodies, or through passive immunisation involving the introduction of antibodies," says Professor Frostegård.
Professor Frostegård believes that such treatment would be suitable especially for high-risk patients, perhaps as a complement to statins. But it is also conceivable, of course, to take a broader approach and carry out preventative vaccinations against atherosclerosis.
"When we´re treating completely healthy people, the bar is raised, you know, when it comes to adverse reactions," says Professor Frostegård.
Text: Cecilia Odlind. Published in Medicinsk Vetenskap nr 1 2010.