972229Development of a novel vaccine for rapid response against PlagueClosedSmall Business Research InitiativeInnovate UKThe aim of this project is to create a novel and innovative vaccine against plague (Yersinia pestis) by using a potent vaccine delivery technology highly suitable for outbreak situations in low-income countries. Plague is a highly contagious and virulent infectious disease transmitted to humans by flea bites. Since the 1990s, the number of human plague cases has increased in 25 countries, and plague is now classified as a re-emerging infectious disease for: 1. the presence of large reservoirs in African, Asian and American continents, 2. its endemicity throughout the world resulting in sporadic infections, including recent outbreaks in the 21st century, 3. the requirement to start antibiotic treatment of pneumonic plague within 24 h after the onset of symptoms (otherwise 100% fatal), 4. its potential use as a bioweapon due to its extreme virulence and ease of spreading (through aerosol), and 5. the recent emergence of antibiotic-resistance strains. Vaccine development efforts against plague have been dominated by the use of live attenuated vaccines and sub-unit proteins. Live attenuated vaccines pose significant safety concerns and the level of protection achieved is debated. Sub-unit proteins in adjuvant have demonstrated a certain degree of protection in animal models, but the immune response seems limited to antibodies while a cellular response correlates with increased efficacy. These vaccines have however greatly contributed to the identification of immune correlates of protection. In this context, our proposed solution is to use viral vectors as a delivery platform. We propose to use this type of vaccine technology, for the first time, based on harmless replication-incompetent viruses, currently developed against numerous infectious diseases including Ebola, malaria and HIV, but not yet investigated for plague. This technology is highly suitable for diseases for which cellular immune response are required for protection, in addition to antibody responses, and is also suited to outbreak situation in low-income countries (as for the recent Ebola outbreak, where all vaccines developed were based on viral vectors). We will use several plague proteins known to elicit protective immune responses and insert them into our latest and most potent viral vaccine vectors, which we found to be highly immunogenic in recent clinical trials including against flu and Ebola. Our group has expertise in delivering bacterial proteins to the immune system by inserting them into such viral vectors including adenovirus (usually responsible for colds) rendered harmless by genetic modification. We will investigate the immune responses and level of protection induced by these novel vaccines in animal models and identify the most potent candidate. If successful, this project will provide a strong case for testing of this new plague vaccine in people