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Periodic Report Summary 1 - VIP (Vaccines and Imaging Partnership)

The ‘Vaccines & Imaging Partnership’ (VIP) is an Industry-Academia Partnerships and Pathways (IAPP) project funded by the European Union under the FP7 Marie Curie Programme. This four-year project (2014 – 2018) represents a collaboration between European universities and the pharmaceutical industry, and focuses on the development of new ways to visualise bacteria in the body, involving scientists from the fields of microbiology, immunology, cancer research and organic chemistry.
VIP activities are being undertaken in the participant institutions at University College Cork, Ireland (Cork Cancer Research Centre and the APC Microbiome Institute); l’École Polytechnique Fédérale de Lausanne, Switzerland; and GlaxoSmithKline Vaccines, Siena, Italy.
There exists an urgent need to advance methods for detection of bacteria in the body, primarily in the context of infectious disease research. By bringing together an international network of leaders in the fields of molecular imaging, infectious disease, vaccine research and industry, VIP addresses the current paucity of technology for imaging of bacteria in research animals. The work programme facilitates transfer of knowledge among project partners, promotes the development and training of staff in both academia and industry, as well as providing the industry partner with new R&D tools.

Project objectives: Optical Imaging (OI) modalities are based on the detection and quantification of bioluminescent or fluorescent light from the subject and represent powerful yet cost-efficient and convenient systems. By labelling of bacteria and/or host cells of interest, both bacterial and host responses can be assessed in rapid, high-throughput analyses, providing spatial, temporal and quantitative read-out, without the need for radioactivity. The project aims to develop improved imaging of bacteria in vivo using optimised reporter gene constructs, novel OI probes, and novel methods of imaging host responses to bacteria. Simultaneously, VIP aims to establish and/or strengthen links between academia and industry in Europe, and to develop staff in industry and academia, while providing them with training in new methods, new technologies, and a range of transferable skills.

Achievements to date:
VIP Bacteria and Models: A biobank has now been decided upon and created, resulting in all partners now working on the same strains. Each imaging approach from each WP is being developed specifically for the VIP bacteria. In vivo infection models have also been optimised for deployment of the various probes.

Novel probes for detection of unmodified bacteria:
Enzyme-based probes: We have identified the nitroreductase (NTR) family of enzymes as ideal candidates for bacterial specific enzymatic activity. Two probes have been developed to date for this enzyme family. We have successfully validated both in vitro and in vivo the utility of these probes with numerous bacteria in a range of infection models. Two publications have resulted.
Chemical probes: We have designed and synthesised a range of fluorescent bacterial-specific probes, that are specifically absorbed by or bind to the surface of bacteria. These are currently being tested in vitro by the partners with the VIP Bacteria Biobank.

Improvement of genetic luminescent reporters: We have developed red shifted luciferase genetic constructs to produce light of the desired wavelength (600nm) for deep tissue imaging. We are also developing novel plasmid constructs to deploy this luciferase cassette to increase the range of bacteria suitable for reporter tagging, with the aim of genetically tagging all the VIP Bacteria Biobank.

Expected final results and potential impact:
We have already and will continue to develop exciting new technologies in optical imaging, enhancing the standing of European research in the area of optical imaging. We expect to add significantly to basic scientific knowledge, to publish the work in high impact journals (2 published to date) and to pursue joint patent applications for nascent technologies. We have established long-term collaborative links between academia and the key commercial company working in this sector (GSK). VIP is providing basic scientists with an opportunity to experience industry secondments, thereby enhancing their career opportunities. VIP activity is attracting world-leading scientists into the area of infectious disease, bioengineering and imaging and providing them with multiple networking and training opportunities and exposure to one of the primary companies working internationally in this arena.
We expect to ultimately impact internationally through the provision of new technologies that will enhance health-care research in the areas of infectious disease and microbial commensalism.

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Life Sciences
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