Enabling rapid conversion of antigen to vaccine, applied to multi-stage malaria vaccination

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Vaccination is one of the most cost-effective ways to save lives and improve health. Despite the great success-stories of many human and animal vaccines, we still lack effective vaccines against major global killers such as malaria, tuberculosis and HIV. New vaccines are often developed from Virus-like particles (VLPs). VLPs resemble viruses in their size and shape, but carry no pathogenic genetic material and so do not cause disease. VLPs can be engineered to display a protein from a pathogen on their surface, to create an effective and safe vaccine. Decorating VLPs with such proteins from pathogens is one of the central challenges in the field of vaccine development, requiring expensive trial-and-error experiments and taking months to years. We have validated initial steps to overcome this key challenge. We engineered a "bacterial superglue" so that decorating VLPs simply requires mixing the VLP with the pathogenic protein. This attachment is fast, irreversible and broadly applicable. Due to the ease of the process, we have termed this platform Plug-and-Display vaccination. The pathogenic proteins we have focused on attaching to VLPs come from the malaria parasite. Malaria is one of the largest global health challenges, each year infecting approximately two million people and killing half a million people. With the difficulty in distributing effective drugs and the increase in drug resistance, there is urgent need to develop a malaria vaccine. We have investigated proteins on the surface of the malaria parasite at different stages of its life cycle and established key targets that could help create a more effective vaccine. In this proposal we will advance the Plug-and-Display vaccination approach in several ways, to maximise the immune responses to these malarial proteins. We will establish the use of our bacterial superglue for decoration of a different kind of VLP frequently used in the clinic. We will create new VLPs able to display three times more copies of the malarial protein, since that could stimulate an even stronger immune response. Also, VLPs will be precisely decorated with two different malarial proteins, to help generate a vaccine effective against a wider range of malaria strains. Since our Plug-and-Display VLPs could be useful not just for malaria but for a range of human and animal diseases, we will also increase the scale and stability of VLPs we produce, so that they can be a general resource for scientists worldwide and speed up the creation of effective vaccines against major health challenges.