A proven foundation: the history of aluminium adjuvants

Vaccine developers today have access to an expanding range of adjuvant technologies. However, aluminium-based adjuvants remain some of the most established and widely used ingredients for vaccine development. Why? Decades of use have allowed time for scientific investigation and development to give researchers a deeper understanding of how antigens and complete vaccine formulations interact with aluminium-containing adjuvants 

Adjuvants are added to vaccines to help enhance the immune response to an antigen. They can support a stronger or more sustained antibody response and, in some cases, reduce the amount of antigen required. The mechanism of action of aluminium-based adjuvants is not yet fully understood despite nearly a century of use. Several mechanisms appear to overlap, and there is consensus that antigen adsorption onto the surface of adjuvant aggregates is an important part of the mechanism sequence. Adsorption may affect antigen stability, highlighting how critical it is to thoroughly investigate interactions between the antigen and adjuvants, alongside buffer type, pH and the inclusion of excipients such as stabilisers. 

Nearly a century after their discovery, the heritage behind today’s Alhydrogel™ and Adju-Phos™ can be traced back to the early industrial production of aluminium adjuvants.  

Alhydrogel™ and Adju-Phos™. Two proven adjuvants. One formulation-led decision. 

Alhydrogel™ (aluminium hydroxide gel) and Adju-Phos™ (aluminium phosphate gel) are two of the most widely used aluminium adjuvants in vaccine development, backed by almost a century of history and impact. 

To understand why aluminium adjuvants remain relevant, it is useful to return to where their story began. 

1926: The year of discovery 
The adjuvant properties of aluminium salts were discovered in 1926 by British immunologist Alexander T. Glenny and his fellow researchers at the Wellcome Physiological Research Laboratories. During their work with diphtheria toxoid, they observed that aluminium salt precipitation produced a stronger antibody response than the soluble toxoid. By 1932, diphtheria vaccines adjuvanted with aluminium salts were administered to children. This was the first use of an adjuvant in human vaccination. 

Aluminium adjuvants changed how vaccine antigens could be presented to the immune system. 

1939: The beginning of Alhydrogel™ manufacturing 
The production of aluminium hydroxide for vaccine use began in April 1939 through a collaboration between Superfos and Statens Serum Institut (SSI). Superfos was a Danish industrial company whose specialist vaccine adjuvant activities began with aluminium hydroxide production. This manufacturing heritage would later become part of Croda Pharma. SSI is an institute under the auspices of the Danish Ministry of Health. SSI’s role has been, and remains, to ensure preparedness against infectious diseases and biological threats. From the beginning, highest medicinal standards have guided development and production of these vaccine adjuvants. 

The roots of Alhydrogel™ go back to the early industrial history of aluminium adjuvants. 

1980: The introduction of Adju-Phos™ 
Forty-one years later, aluminium phosphate entered the market giving developers access to a second aluminium salt adjuvant which expanded formulation possibilities. Under commonly used formulation conditions, Alhydrogel™ typically has a net positive surface charge, while Adju-Phos™ has a net negative surface charge. However, surface charge is not the only deciding factor. Antigen characteristics, pH, buffer composition, stability and the required formulation performance must all be explored. From 1983 the adjuvant business was formally established as a separate business within Superfos, operating under the name of Superfos Biosector. Over the next decade, Biosector became globally recognised for its leadership in vaccine adjuvants. 

1990: A new dedicated adjuvant manufacturing site opens in Frederikssund 
As demand for aluminium adjuvants continued to grow, a new dedicated manufacturing capability was built.  

2000-2001: The Biosector business evolves 
In 2000 Superfos Biosector was acquired along with the rest of the Superfos Chemicals by HCI (Holland Chemicals International), and the business was renamed HCI Biosector. Just one year later, in 2001, Brenntag acquired HCI, leading to another name change: Brenntag Biosector 

2012-2016: Investment in production capacity continues 
A proven platform requires continued investment, rather than relying on history alone. 2012 saw a plant expansion, followed by a new facility and equipment investments in 2016. 

2018: Brenntag Biosector is acquired by Croda Pharma 
Croda acquired Brenntag Biosector and its vaccine adjuvant portfolio, bringing together Biosector’s specialist adjuvant expertise and manufacturing heritage with Croda’s global capabilities in formulation, research and development and technical business development. The combination strengthened access to expertise, local support and formulation guidance, helping vaccine developers make informed decisions throughout the development process.  

Today: A proven foundation for modern vaccine formulation 
A century after the discovery of aluminium adjuvanticity, innovation continues to build on established scientific foundations. As we look to the future, it is important to remember that innovation starts with understanding what works. 

While research continues to deepen our understanding of the adjuvants and their behaviour and mechanisms in a formulation, it must not be underestimated that manufacturing processes play an important role for the efficacy of final vaccine formulation. Manufacturing processes have been optimised over time under the highest pharmaceutical standards. The history of adjuvant manufacturing at Croda Denmark reflects decades of manufacturing excellence and a deep understanding of how to produce consistent high-quality products that meet the stringent requirements of the vaccine industry. 

The science has advanced, but the formulation question remains 

Early exploration of aluminium adjuvants focused on the depot effect, where the antigen was thought to be released gradually at the injection site. Research has since shown that the ways in which aluminium adjuvants support the immune response are more complex. 

Having more options does not automatically make the formulation decision easier. The right starting point depends on factors such as the antigen’s properties, formulation pH, buffer composition, adsorption behaviour and stability. Surface charge can help guide initial selection, but performance must be assessed within the complete formulation. 

Alhydrogel™ and Adju-Phos™ provide two distinct, proven adjuvants for this process. The choice is not simply about selecting an aluminium adjuvant. It is about selecting the adjuvant that best fits the formulation and optimising the formulation characteristics to achieve the required performance. 

In a world full of choices, the answer remains Alhydrogel™ and Adju-Phos™. Two proven adjuvants. One formulation-led decision.