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Alum (1926)

Sometimes in medical science it is not always possible to explain how something works, but only to accept that it does. There is perhaps no better example of this maxim than alum, a mineral salt that dramatically improves the effectiveness of certain vaccines without anyone really knowing why. The technical name for such a substance is “adjuvant” and there are several possible explanations for why they boost the body’s immune response to the antigens of a vaccine.

Alum, an aluminium salt, is the most common vaccine adjuvant and has been used in vaccines for nearly a century. Its benefits for vaccination were first discovered in 1926 by Alexander Thomas Glenny, a British immunologist who worked at the Wellcome Physiological Research Laboratories, then located in central London. Glenny showed that aluminium salts significantly increased the effectiveness of diphtheria toxoid, the vaccine antigens used to protect against diphtheria, when injected into laboratory guinea pigs. He made the breakthrough after observing that animals had a better immune response to the vaccine when the injected toxoid created a localised inflammatory reaction on the skin. So he decided to add substances to the vaccine to deliberately trigger such a response.

Today, alum – potassium aluminium sulphate – is the most widely used human vaccine adjuvant, along with other kinds of aluminium salts such as aluminium hydroxide, aluminium phosphate and mixed aluminium salts. They have a proven safety record from more than 60 years of use, although there have been a few cases of severe localised reactions which have generated largely ungrounded fears over their use in vaccines.

There are several theories that explain how adjuvants work in terms of boosting the immune response to a vaccine. One of them centres on their ability to mimic the conserved molecules found in bacterial or viral pathogens such as liposomes, lipopolysaccharides or fragments of RNA or DNA. The idea is that by adding alum along with the vaccine antigen itself, the inoculation mimics a natural infection. By doing so, it stimulates the immune defences, notably the dendritic cells, to trigger a stronger immune response than the antigen alone –  so making the patient immune to a real infection at a later date.

Despite its long history, however, alum is not the perfect adjuvant. It does not work, for example, with the vaccine antigens designed to provide an immune response against malaria and tuberculosis. Nevertheless, a bottle of alum represents one of the key objects in the history of vaccinology.