New class of molecular adjuvant
Adjuvants are widely used in vaccines to enhance the body’s immunogenic response towards the administered antigen. In recent years, proteins or protein fragments have been trialled as vaccine adjuvants.
Researchers at the University of Oxford have discovered a small immunogenic protein domain, which, when fused to vaccine component antigens, greatly enhances the effectiveness of the vaccine. This approach has proven to be effective in vaccines against S. aureus and P. falciparum, but recent studies, published in scientific reports, also hint at this approach being a more generalised platform technology for the development of new vaccines.
The adjuvant advantage
An adjuvant is a substance that is able to enhance or prolong the body’s antigen-specific immune response to an administered vaccine. Simple inorganic aluminium salts, such as aluminium hydroxide or aluminium phosphate, have been commonly used as adjuvants since the 1930s. Recently, attention has turned to organic or biological adjuvants to tackle more challenging and complex disease targets.
4-Oxalocrotonate tautomerase (4-OT)
4-OT is an enzyme, which forms part of a key metabolic pathway in bacteria. The monomer unit contains just 62 amino-acid residues, making it one of the smallest known enzyme subunits; however, 4-OT forms a hexamer in solution. Researchers at the University of Oxford have been exploring the use of 4-OT proteins as vaccine adjuvants.
Beating the superbugs
The group at Oxford have successfully fused a member of the 4-OT family (SAR1376) to a range of pathogen antigens from Staphylococcus aureus and Plasmodium falciparum. Following delivery of these fused complexes by DNA or viral vectors, increased immunogenicity has been observed in vivo. The 4-OT tag mutimerises in solution and it is the aggregation that is thought to cause the observed increase in immunogenicity. This methodology represents a rare discovery of a non-human multimerisation domain that enhances immunogenicity when fused to a range of antigens.
Perhaps most importantly, 4-OTs are widespread in pathogenic bacteria (both Gram positive and Gram negative). Their conserved structure may allow this to be a generalised approach for enhancing antibody responses to vaccine antigens, offering an attractive alternative to virus like particles (VLPs).
We believe that the key advantages of this technology include:
- Adjuvant shows in vivo efficacy when fused to antigens from S. aureus or P. falciparum
- New platform technology for vaccine development
- Hundreds of potential adjuvants identified in diverse bacterial species
- Rare class of multimerisation tags that can enhance immunogenicity
- Fills need for more antigen scaffolding strategies
Oxford University Innovation Ltd. has filed a patent, which covers this work and is currently seeking a commercial partner to develop the technology.
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