Apoferritin as a virus-like particle for the display of multiple virulence factors for vaccine development

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Vaccines provide an efficient, cost effective method of protecting animals and humans against a large range of pathogens and avoid the need for large scale use of antibiotics and antiviral agents. This reduces the quantities of drugs used to treat infected cattle and minimizes the drug residues and metabolites that can subsequently appear in foodstuffs such as meat, milk or other dairy products. Since the time of Edward Jenner, vaccines have used either whole active benign viruses such as cowpox virus for protection against smallpox infections or chemically or heat-treated pathogenic viruses or bacteria that are unable to replicate/reproduce but produce a protective immune response in the animal being vaccinated. Provided the vaccines are correctly prepared and the virus/pathogen is completely deactivated, this approach works for a number of diseases, but for pathogens such as the influenza virus that rapidly mutates it is necessary to prepare new complex vaccines on an annual basis in order to ensure that the pathogen has not mutated such that it can evade the immune system. In order to make more efficient protective vaccines, researchers have moved away from using deactivated whole pathogens, preferring to generate vaccines based on unique proteins and sugars in them that stimulate both a humoral and cellular immune response. In order to be most effective these structures need to be presented to the immune system in multiple copies on nanoparticles ideally 10-40 nm in diameter and either several different proteins from a single pathogen or several different mutants of the same proteins from a single pathogen need to be presented to the immune system to counteract the changes in the pathogen over time. To achieve this researchers have examined a number of virus and other naturally occurring types of protein capsules and several human vaccines have been generated from these including ones against hepatitis and papillomavirus. We are proposing to use apoferritin as the nanoparticle as it can be produced in large quantities quickly and cheaply with a wide range of pathogen proteins attached. Because apoferritin can self-assemble in to a highly organised protein capsule by changing the pH of the solution, it can be developed into a modular system where large combinations of different antigens can be combined rapidly to generate nanoparticles suitable for vaccination. This would allow new vaccines to be generated rapidly in response to quickly evolving pathogens. To demonstrate the technology we will produce apoferritin-complexes which display proteins from bacteria involved in mastitis infections in cows and goats. Currently in the UK the dairy industry loses milk production equivalent to that of 120,000 cows per year due to mastitis and therefore eradicating this disease would reduce herd sizes freeing up both the land they occupy and the land required to produce their feed for alternative agriculture use. This would also significantly reduce the bovine carbon dioxide generation of the UK.The apoferritin technology could be widely exploited to develop a range of vaccines for both animal and human health.