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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - PHA-ST-TRAIN-VAC (Leveraging Pharmaceutical Sciences and Structural Biology Training to develop 21st Century Vaccines)

Teaser

Summary

Immunisation is one of the most cost-effective and proven tools to control and eliminate infectious diseases, saving millions of lives each year, yet key challenges remain in order to guarantee the future health of the expanding and ageing global population. To meet the challenge of developing vaccines, this EID brings together two cross-sector, world leading teams â€“ GSK Vaccines S.r.L and the University of Strathclyde â€“ with the objective to equip the next generation of vaccinologists with the skills and tools to deliver vaccines for the 21st Century. PHA-ST-TRAIN-VAC has been set up to deliver a unique, multidisciplinary and intersectoral training programme to develop and equip four early stage researchers with the required skills and entrepreneurship to develop new vaccines, in a formulation tailored to the age of the patient.
Our research-led programme will deliver:
1. The development of new vaccines for selected infectious diseases by combining structure-based antigen design, adjuvant design and pharmaceutical formulation.
2. Enhanced vaccine design that uses alternative options for administration able to potentiate immune responses in a format tailored to patient need and the disease in question.
3. The next generation of highly skilled, entrepreneurial researchers with inter-sector, multi-disciplinary skills and expertise to exploit this new research understanding and ensure the delivery of vaccines that can enhance healthcare in the twenty-first century.
4. Enhanced entrepreneurship, creativity and innovation in vaccine design across Europe.
Our training and development plan will deliver:
1. The next generation of highly skilled, entrepreneurial researchers with inter-sector, multi-disciplinary skills and expertise to exploit this new research understanding and ensure the delivery of vaccines that can enhance healthcare in the twenty-first century.
2. Enhanced entrepreneurship, creativity and innovation in vaccine design across Europe.

Work performed

This EID has recruited 4 early stage researchers (ESRs) who have undertaken a range of training activities. This has included research development training and includes consortium wide training, bespoke personalised training packages and operational training, entrepreneurial, management and presentations skills and ethics training. Their research is conducted across three research work packages: 1) knowledge-based modulation of antigen structure and properties, 2) pharmaceutical engineering of adjuvants & delivery systems and 3) assessment of cellular mechanisms and vaccine potency. The 4 ESRs have all completed their first 18 month placement (2 in USTRATH and 2 in GSK) and on the 1st of July 2018 the 4 ESRs swapped locations and moved to their second placement. This allows all 4 ESRs to experience research training in both an academic and industrial context. Each of the ESRs has an individual, personalised research project joint supervised by a multi-disciplinary cross-sector team of at least two supervisors, one from GSKVACSRL and one from USTRATH. Each project has been designed to take full advantage of expertise, methodology and technology available within both sites.
Within this EID we have been using structural vaccinology, to increase the immunogenicity of protein antigens by presenting them in a significantly larger multi-copy format exposed on the surface of bio-nanoparticles. These nanoparticles present a recombinant protein antigen to stimulate broad and efficacious immunogenicity against the encoded antigen. Work has focused on obtaining DNA constructs for the subsequent expression and purification of nanoparticle and recombinant protein antigens. Protein-lipid conjugates have also been designed such that liposome-based systems expressing surface-antigens can be formulated with and without the co-administration of other adjuvants and cloning, expression and purification of proteins has been carried out (WP1). These constructs will now progress into in vitro and in vivo studies (WP3). Within WP2, a range of novel nanoparticles have been developed including lipid-based (liposomes, solid lipid nanoparticles, and lipid-nanoparticles), polymer-based nanoparticles and emulsion systems. Scale-independent manufacturing processes have been identified for each of these adjuvant & delivery platforms. These have been formulated with a range of surface changes and particle size. A selection of cell culture models have been implemented to assess cellular mechanisions in vitro and their biodistribution in vivo has been investigated to correlate physical attributes with clearance profiles. Through these studies we have identifed the key dominant physico-chemical factor dictating their biodistribution after administration (WP3) (Figure 1).

Final results

The research from this EID has already been disseminated through a range of conferences and poster presentations and research publications are being developed. The scalable manufacturing platforms developed within this EID are applicable to a wide range of particulate adjuvants and also nanomedicines so will have a wide benefit to the pharmaceutical industry and the academic sector. There is an already sizeable market in the global healthcare sector for nanomedicine. With a current market value of $135 billion (â€œTrends in Nanomedicineâ€ by Frost & Sullivan, December 2015), and Nanomedicines are one of the six Key Enabling Technologies listed in the Horizon 2020 EU industrial funding schemes that are predicted to have the most significant impact on the on the healthcare sector. A key challenge preventing the successful commercialisation is mainly attributed to the cost of production in large-scale industrial settings. Thus this EID has already addressed this challenge and commercialisation of these new manufacturing methods is currently being considered. Similarly, the bio-conjugation steps being used in the development of the bio-nanoparticles and the protein conjugates have wider application in the nanoparticle field and this will be shared one appropriate IP is in place.
To disseminate our research we have also undertaken a range of public engagements through this EID. Social media is recognised as a key communication platform and this EID has set up a dedicated website and social media account @PhastTrainVAC.
The research from PHA-ST-TRAIN-VAC, and the positive impact of vaccination, has also been promoted widely on various social media platforms via the University media outlets including YouTube, Facebook, Twitter and Flicktr. This was achieved through an â€˜Images of Researchâ€™ campaign. The ESR team based in USTRATH developed a research story board, based on their research as part of an annual competition. This resulted in their work featuring in a year-long exhibition brings the research conducted at Strathclyde to an audience of thousands of people visiting art galleries, museums and public spaces (see @strathImages and https://www.imagesofresearch.strath.ac.uk/index.php for further details).

This EID has also undertaken outreach activities including â€œExplorathonâ€ to share and promote the work of PHA-ST-TRAIN-VAC This involves public engagement activities taking place in a variety of venues, with the aim of reaching 4,000 members of the public on a 1:1 basis. The ESRs based in USTRATH, organised a science outreach event at a local primary school.