Researchers have shown how 'alum' adjuvants make vaccines more effective

Researchers based in the Netherlands and Belgium have worked out how aluminium salts - widely used to boost the effectiveness of vaccines - stimulate the immune system. 

Adjuvants such as aluminium hydroxide or phosphate, collectively referred to as ’alum’ by doctors, are commonly added to vaccines to boost the production of antibody. But exactly how they work is not known. 

Now, the group of Bart Lambrecht at the Erasmus University Medical Centre in Rotterdam, Netherlands, together with colleagues at the University of Ghent, Belgium, have found that aluminium hydroxide stimulates dendritic cells - responsible for kicking-off the body’s immune response. 

Previous studies had shown that the compound had no effect on these white blood cells in vitro. But when Lambrecht’s group examined the adjuvant’s effect on mice[1], they found it did stimulate them indirectly - by triggering the release of uric acid, which acts as a chemical danger signal in the body. 

The group found that aluminium hydroxide kills a small number of cells when it is injected. These dying cells produce uric acid - the key ingredient that was missing from the earlier in vitro studies - which increases the response of mouse dendritic cells to the vaccine. 

An earlier paper in Science had also described in vivo consequences of alum injection, [2] but Lambrecht believes that his work has uncovered the root of the immune system’s response to adjuvants. ’The Science paper describes what happens in the spleen a week after the injection,’ says. ’But we have shown the immediate reaction.’ 

Lambrecht hopes that his results will help to develop improved vaccines. ’One annoying thing about the existing adjuvants is that they don’t activate the cellular immune response very well,’ he says. ’In our current research, we are trying to modify the uric acid response to improve that.’ He points out that his research supports earlier suggestions that uric acid itself could be used as an adjuvant instead of aluminium salts - perhaps removing the pain that some patients feel after vaccination.

Jonathan Austyn, a professor of immunobiology at the University of Oxford praised the work, but doesn’t think the study completely explains how adjuvants work. ’Lambrecht et al haven’t definitively shown how uric acid is involved in the phenomenon,’ Austyn says. 

Michael Gross