972221Polyhedrin-encased glycoproteins as novel cold chain independent vaccinesClosedSmall Business Research InitiativeInnovate UKThe majority of vaccines have a narrow temperature window within which they must be stored to maintain functionality. The development of vaccines that are stable at ambient temperatures is a major challenge in their delivery to the people that need them the most, in low-income settings where the refrigeration infrastructure required is poor. We have developed an innovative vaccine manufacturing system, based on a patented protein production mechanism. This system exploits the unique properties of the polyhedrin protein naturally expressed by the silkworm (Bombyx mori) cypovirus. The polyhedrin protein forms large, temperature-stable and pH-stable crystals within infected insect cells. These crystals attach to, and subsequently encase, mature cypovirus virions. This results in enhanced stability and viability of the virion, leading to a markedly longer window of infectivity. Genetic engineering techniques have been used to adapt this viral survival mechanism to encapsulate any given tagged recombinant proteins by co-expression with polyhedrin protein. This in-vitro insect cell expression system is known as PODS (POlyhedra Delivery System). PODS provides key advantages for vaccine production, including (1) rapid development, to address emerging viruses, (2) scalability of manufacture, and (3) inherent stability of cargo protein structure, even over extended periods in warm and wet conditions, eliminating the need for cold-chain supply and the need for frequently repeated, more costly manufacturing schedules. The aim of this study is to develop a vaccine delivery platform based on PODS. The project will have 3 streams: 1) Develop PODS encoding and encapsulating glycoproteins from a range of priority pathogens with pandemic potential and confirm temperature stability of PODS vaccines over an extended time. 2) Test PODS for their ability to induce neutralising antibodies. 3) As a proof of concept, test PODS vaccines for their ability to protect against infection. We will examine three viral infections based on prioritization by UKVRDN and based on our expertise: (1) Zika virus, an emerging pathogen linked to malformation of the brain in children of mothers infected during pregnancy. (2) Ebola virus, a viral hemorrhagic fever that has caused the death of >11,000 individuals in West Africa since December 2013. (3) Lassa fever, an acute viral haemorrhagic illness that is endemic in the rodent population in parts of West Africa which causes illness in 300,000 individuals each year with around 5,000 deaths as a result. By the end of these initial studies, we aim to obtain proof of concept that the PODS platform can be used to generate temperature stable vaccines capable of inducing a potent neutralising antibody response. Having shown the efficacy of the vaccine we plan to move to GMP production of PODS in a phase II application.