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What are adjuvants?

Adjuvants, named from the latin word “adiuvare” meaning “to aid,” are important substances that can strengthen the immune responses of various vaccine formulations.

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Adjuvants have been used for decades to help enhance the immune response to vaccine antigens. 

Most of us understand the fundamentals of vaccines: introduce part of a pathogen to our immune system, in order to elicit a specific, lasting immune response that protects us from a future infection.

Adjuvants are vaccine ingredients that can help induce a strong immune response in certain formulations. Today, aluminum salts are the most widely used adjuvants, whilst scientists and vaccine manufacturers are continuously innovating to expand the repertoire of available adjuvant options.

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A short history of vaccine adjuvants

The story begins in 1920 with Gaston Ramon, a French veterinarian working on a new diphtheria vaccine. He made an accidental discovery: horses that developed ghastly abscesses at the injection site also had stronger immune responses.

This made him wonder: what else could be added to the vaccine to spur such a reaction?

In order to confirm his hypothesis, he used a combination of inactivated toxin, together with starch or breadcrumbs, to induce sterile abscesses at the injection site.

These experiments proved a success: animals administered vaccines that contained Ramon's concoctions produced significantly more antibodies compared to those who didn't. Thus, they were thought to be better protected against diphtheria - and unveiled the field of adjuvants!

image of woman in a lab formulating with an adjuvant system

Aluminium adjuvant discovery

Alexander Glenny, a British immunologist, was the first to document the adjuvant effect of aluminium compounds in 1926. After using aluminium salts to purify diphtheria toxoids (inactive toxin), Glenny incorporated potassium aluminium sulfate in vaccine production. To his surprise, the aluminium salt precipitation significantly increased the immune response against the toxoids in guinea pigs. Adding aluminium salts created a localised inflammatory reaction on the skin that strengthened vaccine success.

This breakthrough forever changed vaccine development. Vaccines prepared in this way are known as alum-precipitated vaccines. However, they weren’t without pitfalls. Not only could they be highly heterogenous, but batch reproducibility was difficult and there was a lack of control of the amount of antigen.

Today, after many years of research, manufacturing of aluminium adjuvants has been optimised and advanced to the highest standards.

No wonder "alum" adjuvants continue to be the most widely used worldwide!
scientist in lab formulating with adjuvants

Saponin-based adjuvants

The high potential of saponin-based adjuvants had been recognised going back to vaccination studies carried out by Gaston Ramon, a French veterinarian, in 1925. Dr. Kristian Dalsgaard successfully purified and characterised a mixture of saponins from the bark of Quillaja saponaria Molina known as Quil-A® in 1974. Quil-A has since been used as a highly performing adjuvant in numerous veterinary vaccines. 

Finally, the isolation of a defined fraction of the saponin mixture enabled usage of saponins in human vaccines. In 1991, Dr. Charlotte Kensil et al. isolated and named QS-21 as a component of the triterpenoid quillaja saponins comprising different isomeric forms. QS-21 demonstrated an optimal balance of enhanced immunostimulatory properties and tolerable reactogenicity and has already been used in one commercialised vaccine. QS-21 is part of our offer and available for investigational use. 

What are adjuvants used for?

Adjuvants are used in vaccine design to accelerate, prolong, or enhance immune responses. They can help to raise an early, long-lasting and efficient immune response to the vaccine. This increases vaccine efficacy and can provide a high degree of protection from the disease against which you are vaccinating.

What are the advantages of adjuvants?

Adjuvant systems can help reach the same level of immune protection with fewer injections or a lower dose than when vaccinating with the non-adjuvanted antigen alone.

Some vaccine formulations do not result in optimal antigen delivery and presentation thereby reducing vaccine efficacy. Thus, a diverse repertoire of adjuvant systems is necessary to create better vaccines.

How do adjuvants increase vaccine efficacy?

Adjuvant systems stimulate immunity at various stages of the immune response, e.g. by activating chemokine signalling and targeting specific types of immune cells, such as dendritic cells and T-helper cells (Th1, Th2 or Th17).

Nevertheless, ongoing research is working towards unraveling the precise mechanisms of action of adjuvant systems.

What are the types of different adjuvants?

Adjuvant systems can be classified according to their physical and chemical properties, as well as their functions. These functions can be as vaccine delivery systems or immunostimulators.

Notable examples include aluminium salts, oil emulsions, saponins or TLR agonists.

Do all vaccines contain adjuvants?

Not all vaccines contain adjuvants, such as those based on an inactivated virus or bacteria. Still, most modern and current vaccines feature adjuvant systems. Aluminium salts are found in almost all DTP vaccines, as well as Hep-A, HPV and anthrax vaccines.
Recent vaccines against challenging pathogens contain lipid delivery systems with specific TLR-agonist immunostimulators (MPLA.) For instance, AS01 is used in the vaccine against varicella zoster and AS04 in the HPV vaccine.

What are the emerging adjuvant technologies?

Modern vaccinology has seen tremendous growth over the last few decades, leading to new and improved technologies that can induce a wider breadth of protection and address an assortment of conditions. The next-generation of vaccines will focus on, among others, liposomal adjuvants like CAF01 and CAF09b, as well as TLR4 agonists (such as PHAD, 3D-PHAD and 3D(6-acyl)-PHAD).

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