FLIP Expression of recombinant target antigens for neglected tropical diseases in surrogate organisms

Lead Research Organisation: University of Kent
Department Name: Sch of Biosciences

Abstract

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Technical Summary

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Planned Impact

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Publications

10 25 50
 
Description Despite the massive expansion of technologies and biotherapeutic drugs over he last 20+ years, little of this enormous effort, either at the drug target or drug product level, or at the level of developing novel expression technologies for difficult to express proteins, has focussed upon application of such approaches and technologies to developing new drugs, detection and diagnostic tools, or expression systems for biotherapeutics in the area of neglected tropical diseases. One such example is the in the area of human African Trypanosomiasis (HAT, sleeping sickness). This disease threatens millions of people in the sub-Saharan area of Africa. The development of new, more reliable and economic diagnostic biomarkers and assays is essential, particularly for distinguishing between early and late stages of the disease to inform the drug regimen used if this disease is to be reduced further in the sub-Saharan. As such, some recent developments in this area have focussed upon identification and validation of new diagnostic markers of HAT to complement or improve upon the current Card Agglutination Test for Trypanosomiasis (CATT), whilst others continue to investigate the possibility of developing a vaccination to this disease. Hence, for both the development of new diagnostics and for potential new vaccines, the availability of appropriate expression systems for the generation of recombinant protein molecules is required.

He we have used existing expression systems and applied them to new areas of need/challenges with a view to create a new platform technology which could be used for tropical zoonotic diseases.

So far through the project we have
1. Established a collaboration between the University of Kent and the charity Medecins Sans Frontieres (MSF).
2. Established the LEXSY expression system in the laboratory at Kent for the generation of novel antigens to use in new diagnostics for HAT.
3. Generated appropriate constructs for HAT antigens, and constructs for a model IgA for expression in the LEXSY expression system (Leishmania).
4. Undertake preliminary expression of the model antigen proteins by transforming Leishmania cells by electroporation and purifying the expressed proteins by His tag chromatography (for the tagged HAT antigens).
5. Begun to characterise the glycosylation of model proteins produced in LEXSY cells.
6. Begun to assess the antigenic properties of these targets in collaboration with the Tropical Institute of Medicine in Belgium.
8. Development of an ELSIA based diagnostic for HAT.

The overall objective is for the development of new HAT diagnostics in the field. We are now taking the findings further forward using a follow-on-fund grant to commercialise the technology.
Exploitation Route These findings will be able to be developed by others in the field looking to develop new rapid, pint of care and low cost diagnostics for tropical diseases, specifically for HAT.
Sectors Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description The project has developed new antigens for the use in diagnostics for human African Trypanosomiasis (HAT, sleeping sickness). These were evaluated in collaboration with the tropical medicine institute in Belgium who have provided access to appropriate samples. This showed that these antigens gave superior diagnostic capability over current antigens. These findings are now being taken forward and developed further to investigate the development of new diagnostics for use in the field. A clinical trial with the new diagnostic is now underway in Africa and will be complete in the next 18-24 months.
Sector Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Cultural,Societal,Economic

 
Description Folow-on-Fund
Amount £190,760 (GBP)
Funding ID BB/NO12496/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 12/2015 
End 01/2018
 
Description Tropical Institute Collaboration 
Organisation Institute of Tropical Medicine Antwerp
Country Belgium 
Sector Academic/University 
PI Contribution Development of recombinant antigens for rapid diagnostic test for sleeping sickness.
Collaborator Contribution Providing serum and samples to test and validate antigens and diagnostics.
Impact Development of new diagnostic for sleeping sickness that is now in field trial in Africa.
Start Year 2014
 
Title A second generation Rapid Diagnostic Test (RDT) for Human African Trypanosomiasis (HAT) 
Description Currently in trial in Africa and being tested against other diagnostics to determine if the one developed during this project is superior. 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Late clinical evaluation
Year Development Stage Completed 2017
Development Status Under active development/distribution
Clinical Trial? Yes
UKCRN/ISCTN Identifier Not known
Impact Outreach and Dr Barrie Rooney awarded BBSRC Social Innovator of year. 
 
Company Name Trozon X 
Description The PDRA on the project has developed this spin out project and is the CEO. The aim of TROZON X is to design diagnostics for Tropical Zone Diseases which are easy to use in any environment. 
Year Established 2017 
Impact None yet.
Website http://www.trozonx.com
 
Description 7 open days at University 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Describing the research we undertake in the laboratory, covering all aspects of the research and the impact this has/can have. Particular questions around genetic modification of cells to produce recombinant proteins in all sessions and discussions around both the ethical aspects of this and the potential applications of such technology.
Year(s) Of Engagement Activity 2015,2016
 
Description Barrie Rooney spoke on BBC Radio Kent about working in Africa with contagious diseases 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Discussion afterwards.

Asked about tropical diseases.
Year(s) Of Engagement Activity 2014
URL http://www.bbc.co.uk/programmes/p027d7jt
 
Description Chartham primary school science day 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact 150 primary school children got hands-on experience of how science integrates into everyday life. The teachers said the children found it really interesting.
Year(s) Of Engagement Activity 2018
 
Description Open Day Activities 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Activity involved practical demonstration of cell culture and gene editing. Also involved demonstration of mass spectrometry to determine post-translational modifications of proteins. Major activity was describing how engineering of cells can be used to produce recombinant biotherapeutic drugs.
Year(s) Of Engagement Activity 2018
 
Description Open Days At University 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact This activity is take take parents and secondary students around my research laboratories to explain the research undertaken and to demonstrate some of the research that we do in the laboratory.

Parents and students asked about engineering of cell lines and therapeutic recombinant protein drugs and how these are made, cost implications and on-going research.
Year(s) Of Engagement Activity 2007,2008,2009,2010,2011
 
Description Outreach Presentation on Diagnostics for Neglected Tropical Diseases 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Rotary Club Presentation on Diagnostics
Year(s) Of Engagement Activity 2016
 
Description Royal Society Summer Science Exhibition 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact The Summer Science Exhibition is an annual display of the most cutting-edge science and technology in the UK. This free, week-long festival features exhibits and a series of inspiring talks and activities for all ages. Meet the scientists, discover the exciting research and technology they work on and have fun with great hands-on activities.
Year(s) Of Engagement Activity 2018
URL https://royalsociety.org/science-events-and-lectures/2019/summer-science-exhibition/
 
Description School visit/outreach for several days at Simon Langton Boys Grammar - MBP2 project showing students how to clone, express and purify recombinant proteins in the laboratory and discuss science behind this. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Helping with research activity in school - cloning and expression of recombinant proteins
Year(s) Of Engagement Activity 2015,2016
 
Description Turkey Public Biotechnology Talk 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Presentation to public audience in Turkey on behalf of the British Council around biotechnology and its application. Event was filmed and followed by a question and answer session, answering questions sent in before the talk by social media and then from the audience. The event was filmed and shown on national TV in Turkey. Large range of topics discussed around the application of biotechnology to every day life and issues with long discussion/debate.
Year(s) Of Engagement Activity 2016
URL http://www.britishcouncil.org.tr/en/programmes/education/science-innovation-talks/biotechnology