Inflammatory induction by vaccine adjuvants with special focus on aluminium adjuvants
- Contact person:
- Håkan Eriksson
- British Medical Research Council (MRC)
- Responsible at Malmö University:
- Håkan Eriksson
- Project members:
- Prof. Peter Siesjö - Department of Clinical Sciences - BMC - Lund University
- Prof. Christopher Exley - Keele University - UK
- Time frame:
- 01 January 2010 - 30 June 2021
- Research subject:
About the project
The immune system protects the body from pathogenic microorganisms such as virus and bacteria and our immune system is capable of discriminating between infectious agents and our own cells, resulting in the specific elimination of pathogens upon infection. During an immune reaction, several distinct cell types, each having a specific function, are involved and collaborate to efficiently eliminate the pathogen. Briefly the immune system can be divided into sentinel cells and effector cells. Monocytes, neutrophils and dendritic cells are all sentinel cells, and they circulate the body and sample screen their surroundings for foreign materials.
These cells are also called antigen-presenting cells (APCs) and are capable of recognising the infectious agent and alerting other cells of the immune system. APCs initiate the immune response which results in maturation of effector cells, such as B and T cells.
Sentinel cells or APCs are extremely good at removing cell debris and foreign material by a process called endocytosis and these cells are pivotal for the development of a protective immune reaction. APCs are the major target cell population of a vaccine.
Vaccination is probably one of the greatest medical achievements and to improve the effect of a vaccine, adjuvants are often included in the vaccine formulation. An adjuvant is a molecule that potentiates the immune response induced by the vaccine, and commonly used adjuvants in vaccine formulations are aluminium salts as aluminiumoxyhydroxide and aluminiumhydroxy-phosphate. In spite of the extensive use of these mineral adjuvants since the 1920s, it is still not known exactly how they work. Other forms of adjuvant used in pharmaceutical and experimental vaccine formulations are danger associated molecular patterns (DAMPs) or analogues hereof such as CpG and monophosphoryl lipid A (MPL), which target toll like receptors (TLRs).
An inflammatory reaction is the basis of an immune response and adjuvants induce a pro-inflammatory response attracting and activating APCs. The aim of this project is to investigate the pro-inflammatory mechanisms induced by adjuvants having a special focus on inflammatory signals induced after cellular endocytosis and engulfment of aluminium adjuvants.
* Mile,I., Svensson,A., Darabi,A., Mold,M., Siesjö, P. and Eriksson,H., Al adjuvants can be tracked in viable cells by lumogallion staining
J. Immunol. Meth., 422, 87-94, 2015
* Mold,M., Eriksson,H., Siesjö,P., Darabi,A., Shardlow,E. and Exley.C., Unequivocal identification of intracellular aluminium adjuvant in a monocytic THP-1 cell line.
Scientific Reports, 4, 6287-6293, 2014
* Ohlsson,L., Exley,C., Darabi,A., Sandén,E., Siesjö,P. and Eriksson,H. Aluminium based adjuvants and their effects on mitochondria and lysosomes of phagocytosing cells
J. Inorganic Biochemistry, 128, 229-236, 2013
* Hellman,P. Andersson,L., Cirkic,E. and Eriksson,H., Myeloid blood dendritic cells and monocyte-derived dendritic cells differ in their endocytosing capability
Human Immunology, 73, 1073-1081, 2012
* Exley,C., Siesjö,P. and Eriksson,H., The immunobiology of aluminium adjuvants: how do the really work?
Trends in Immunology, 31, 103-109, 2010
* Hellman,P., Andersson,L. and Eriksson,H., Ligand surface density is important for efficient capture of immunoglobulin and phosphatidylcholine coated particles by human peripheral dendritic cells
Cellular Immunology, 258, 123-130, 2009
* Andersson, L., Hellman,P. and Eriksson,H., Receptor-mediated endocytosis of particles by peripheral dendritic cells
Human Immunology, 69, 625-633, 2008
* Andersson,L. and Eriksson,H. De-aluminated zeolite Y as a Tool to Study Endocytosis, A Delivery System Revealing Differences between Human Peripheral Dendritic Cells
Scand. J Immun., 66, 52-61, 2007
* Hellman, P. and Eriksson,H. Early activation markers expressed by human peripheral dendritic cells
Human Immunology, 68,3 24-333. 2007
* Dahm,Å. and Eriksson,H. Ultra-stable zeolites – a tool for in-cell chemistry J. Biotechnology, 111, 279-290, 2004