Publication in Nature Medicine
The teams of Doctor Christophe Desmet and Professor Fabrice Bureau, of the Laboratory of Cellular and Molecular Physiology within the University of Liège’s GIGA-Research centre, and of Professor Ken Ishii at the University of Osaka in Japan have just discovered an unexpected mode of action for the vaccine adjuvant alum. Indeed, it seems that when a vaccine containing alum is injected, contact with alum pushes certain cells of the body to release their own DNA. The presence of this DNA outside the cells, a place where it is not to be found in normal conditions, thus acts as a stimulant of the immune system and strongly boosts the response to the vaccine.
Alum, a salt of aluminium, is currently by far the most widely used vaccine adjuvant. Developed in the middle of the 20th century, alum has largely demonstrated its effectiveness and safety of use. That it is why it is found in numerous vaccines. Tens of millions of doses of alum are thus administered each year, and each person in our Western societies has probably received alum at least once in their life. Nevertheless, alum was developed in a relatively empirical manner; the way it helps the immune system to respond to vaccines had not been properly understood up until now.
The discovery by the Belgian and Japanese researchers thus enables a better understanding of the way current vaccines work, and should help in the creation of new adjuvants for future vaccines. The response mechanisms to DNA brought to light in this study could in particular eventually allow the development of new adjuvants with extremely targeted and effective activity.
The researchers are this week publishing their results in the journal Nature Medicine.
« DNA released from host cells mediates aluminum adjuvant activity », Nature Medicine, doi: 10.1038/nm.2403
Thomas Marichal1,2, Keiichi Ohata3, Denis Bedoret1,2, Claire Mesnil1,2, Catherine Sabatel1,2, Kouji Kobiyama3,4, Pierre Lekeux1,2, Cevayir Coban3, Shizuo Akira3, Ken J Ishii3,4,5, Fabrice Bureau1,2,5 & Christophe J Desmet1,2,5
1Laboratory of Cellular and Molecular Physiology, Groupe Interdisiplinaire de Génoprotéomique Appliquée (GIGA), University of Liège, Liège, Belgium.
2Laboratory of Biochemistry, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
3World Premier International Immunology Frontier Research Center, Osaka University, Osaka, Japan.
4Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Osaka, Japan.
A confocal microscope photograph of DNA released by cells in contact with alum contained in a vaccine. The DNA is ‘coloured’ blue by a chemical molecule that binds to it when it exits the cells, thereby making it fluorescent.
© GIGA Université de Liège www.giga.ulg.ac.be
Why adjuvants in vaccines?
Vaccines constitute one of the most effective weapons of modern medicine to prevent the emergence of serious infectious diseases such as poliomyelitis, hepatitis B, diphtheria and tetanus. Vaccination has in particular led to the complete eradication of genuine scourges such as smallpox, responsible for tens of millions of deaths. Today there are great hopes of being able to create vaccines against other great scourges of humanity, such as malaria, the AIDS virus, and even certain types of cancer. These steps forward require important progress in various areas, notably in the in depth understanding of the mechanisms of vaccination.
A vaccine is a preparation containing, a killed or weakened form, certain components or a synthetic substitute of an infectious agent (virus, bacteria) responsible for a disease. In stimulating it the vaccine ‘prepares’ our immune system to defend itself against a given infectious agent. It thus offers us protection against the disease that the latter could cause. Certain preparations of infectious agents are completed by an adjuvant, for instance if they do not by themselves stimulate the immune system sufficiently. A vaccine adjuvant is a substance capable of increasing the immune response activated by a vaccine. Alum, an aluminium salt, is currently by far the most used adjuvant.
Pr Fabrice Bureau et Dr Christophe Desmet, Université de Liège, GIGA, Laboratoire de Physiologie Cellulaire et Moléculaire