With an estimated 100 million sharks killed globally each year, concerns are growing over the long-term survival of the deep-sea predators. Sharks are valued for squalene, a compound found in shark liver and used in health supplements and cosmetics. Squalene is also used in formulations of human vaccine adjuvants, which boost the body’s immune system.
The University of Nottingham has been selected to partner with the Infectious Disease Research Institute (IDRI) and biotech company, Amyris Inc. to find sustainable alternatives to shark squalene to use as vaccine adjuvants.
The project is funded by a $4.4m, five-year grant (#R01AI135673) to IDRI from the U.S. National Institute of Allergy and Infectious Diseases (part of the U.S. National Institutes of Health).
The objective of the project is to discover and evaluate novel biosynthetic molecules produced by bioengineering and chemical engineering approaches for vaccine adjuvant applications. The funding comes from a special bioengineering research grant aimed at enabling engineering expertise to tackle a biomedical problem and ultimately develop a new solution.
IDRI has selected Amyris and the University of Nottingham as partners because of their individual successes in engineering pure molecules from sustainable sources at low cost.
Nottingham project lead, Professor Derek Irvine, from the Faculty of Engineering, said: "While shark liver oil is the world's richest natural source of squalene, frequently used as an ingredient by pharmaceutical and cosmetic industries, the supply is unsustainable and of great environmental concern. This project to find synthetic alternatives to squalene is a fantastic opportunity to use controlled polymerisation to deliver real social impact.”
The Nottingham-based research will examine the molecular properties and structures of monomers and the polymers made from them to make a vaccine that boosts immune responses to proteins known as antigens and to understand what role adjuvants, such as squalene, play in that process.
The aim is to build polymers from a broad range of monomers which can now be either manufactured from sustainable starting materials using “green chemistry” approaches (e.g. isoprene) or extracted from agricultural and forestry waste products such as tree bark or fruit peel (e.g. terpenes).
“It will not only deliver a step chain in the security of supply for essential vaccines but will also significantly reduce the environmental footprint of vaccine manufacture," adds Professor Irvine, a materials chemistry specialist.
While one of the goals of this project is to find a replacement for the pharmaceutical squalene derived from sharks, there are other key drivers. “We want to understand how squalene formulations actually work as adjuvants,” said Christopher Fox, PhD, Vice President of Formulations at IDRI and principal investigator for the project.
“By generating compounds with various structural alterations, we can study the structure-function relationship of squalene-like molecules and shine a light on their mechanisms of action.”
Fox added that key attributes of adjuvants in vaccines are the ability to improve an immune response and minimize the dose of vaccine necessary to confer immunity, which is particularly important where there is a disease outbreak that results in a vaccine shortage.
“Development of this technology could enable formulations that effectively increase the number of vaccine doses available in the event of an influenza pandemic,” Fox said.