Tropical Infectious Disease Consortium: Expanding and Accelerating Product Development

Lead Research Organisation: Liverpool School of Tropical Medicine
Department Name: UNLISTED

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Technical Summary

The Tropical Infectious Disease Consortium (TIDC) has been leading the way in turning fundamental discoveries into improvements in human health and economic benefit for tropical diseases since its establishment in 2013. The Consortium brings together much of the UK’s expertise in tropical infectious diseases into a single translational partnership from Liverpool School of Tropical Medicine (LSTM), London School of Hygiene and Tropical Medicine (LSHTM), the Jenner Institute at Oxford University (Jenner) and Public Health England (PHE). TIDC is strategically placed to deliver an unprecedented portfolio of domain specific expertise in all the key research areas of interest.

Over the past five years, the Consortium has attracted 148 applications that the External Scientific Advisory Committee (ESAC) found to be highly competitive and fundable. Of these 148 projects, the Consortium was only able to award the top 66 scoring projects (less than 50%), 31 of which included collaborations within the Consortium, 30 included partners external to the Consortium, and 47 involved industrial partners. The funded themes have so far included; 21 vaccines development projects (including an evaluation of a Zika virus fowlpoxbased vaccine), 18 drug/biologics discovery projects, 16 diagnostic discovery/development projects (including AMR), 7 new insecticide resistance, surveillance and control tools, 3 anti-venom therapies, 2 adjunct therapy projects and 1 intervention (bed nets).

To date, the consortium has received approx. £2.8 million in funding that has realised just under £40 million in follow-on funding from 31 out of the 66 funded projects. Follow-on funding has been received from both UK sources e.g. MRC, Innovate UK, Department for International Development (DFID), Wellcome Trust, NHIR, and international funders e.g. Bill & Melinda Gates Foundation, Industry and product development (PDPs) agencies. It is our view that these project awards confirm the national and international excellence and calibre of the investigators, their partnerships and projects.

The Tropical Infectious Disease Consortium requires continued CiC funding to sustain and expand on these important, innovative multi-institutional translational projects that are leading the way in addressing global needs. The Consortium has seen a steady rise in highly competitive applications since 2013 meaning that we are not able to fund even 50% of applications due to limited resource allocation. Further increased CiC investment will contribute to drive innovation, speed up the transfer of the best ideas into new interventions, and improve the return on investment in fundamental research. We are best placed to achieve this by broadening the range of technology platforms and translational expertise within the four participating institutions, catalysing and enhancing future translational projects, and leveraging expertise from the four institutions into a powerful “virtual” discovery and development engine for the UK.

Publications

10 25 50
 
Description Discovery and early translation of small molecule toxin inhibitors for use as broadly effective, inexpensive, oral, prehospital snakebite treatments
Amount £2,621,953 (GBP)
Funding ID 221712/Z/20/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2021 
End 03/2025
 
Description Exapnding Excellence in England 'Centre for Drugs and Diagnostics'
Amount £9,843,478 (GBP)
Organisation United Kingdom Research and Innovation 
Sector Public
Country United Kingdom
Start 07/2024 
End 07/2029
 
Description Institutional Partnership Awards 'LSTM translational enabler'
Amount £300,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2022 
End 03/2023
 
Description Target Malaria - Phase II
Amount $2,724,003 (USD)
Organisation Imperial College London 
Sector Academic/University
Country United Kingdom
Start 09/2021 
End 06/2022
 
Description The therapeutic potential of targeting bioactive lipids in filariasis
Amount £1,663,652 (GBP)
Funding ID MR/X001911/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 07/2022 
End 07/2027
 
Description UKRI MRC Impact Acceleration Accounts (IAA) Scheme 'Tropical Infectious Disease Consortium: Expanding and Accelerating Product Development
Amount £306,774 (GBP)
Organisation United Kingdom Research and Innovation 
Sector Public
Country United Kingdom
Start 03/2023 
End 03/2026
 
Description Biomarkers of covert lymphoedema in bancroftian filariasis 
Organisation James Cook University
Country Australia 
Sector Academic/University 
PI Contribution Targeted multiplex plasma biomarker assays to identify inflammatory and angiogenic molecules associated with early filarial pathology (pre-lymphoedema / covert lymphoedema Hosting and training of James Cook and Myanmar MoH personnel (technology exchange)
Collaborator Contribution Field-based longitudinal (pre and post treatment) epidemiological and pathology studies of an endemic cohort of bancroftian filariasis patients in Myanmar Provision of field samples - human, acellular plasma for immunological analysis
Impact NA
Start Year 2015
 
Description Biomarkers of covert lymphoedema in bancroftian filariasis 
Organisation Ministry of Health and Sports
Country Myanmar 
Sector Public 
PI Contribution Targeted multiplex plasma biomarker assays to identify inflammatory and angiogenic molecules associated with early filarial pathology (pre-lymphoedema / covert lymphoedema Hosting and training of James Cook and Myanmar MoH personnel (technology exchange)
Collaborator Contribution Field-based longitudinal (pre and post treatment) epidemiological and pathology studies of an endemic cohort of bancroftian filariasis patients in Myanmar Provision of field samples - human, acellular plasma for immunological analysis
Impact NA
Start Year 2015
 
Description Centre for Excellence in Infectious Disease Research Innovations 
Organisation Centre for Excellence in Infectious Disease Research Innovations
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution We have provided unpublished data under CDA and discussed potential collaborations with animal healthcare companies
Collaborator Contribution CEIDRi have engaged with three animal healthcare companies (Ceva, Elanco, Merck) to foster potential partnerships to utilise our innovations in preclinical model systems for anti-filarial research and development and to develop anti-Wolbachia drugs for animal filariasis indications
Impact Service agreement with Ceva Animal Health negotiations with Elanco Animal Health to sub-licence existing IP
Start Year 2019
 
Description MRC DPFS Biomedical Catalyst Pre-Clinical Development of Small Molecule anti-Wolbachia Candidate Macrofilaricide Drugs MRC Reference: MR/R007403/1 
Organisation University of Liverpool
Department Department of Chemistry
Country United Kingdom 
Sector Academic/University 
PI Contribution Preclinical testing of the candidate anti-Wolbachia antibiotic macrofilaricide AWZ1066 utilising models developed as part of the NC3Rs studentship
Collaborator Contribution medicinal chemistry, toxicology, pharmacology
Impact none so far
Start Year 2018
 
Description New snakebite therapeutics partnership with Johnson and Johnson 
Organisation Johnson & Johnson
Country United States 
Sector Private 
PI Contribution We are establishing a screening platform that we will use compounds provided by our partners in, to determine their inhibitory potential as new snakebite therapeutics.
Collaborator Contribution They have provided two 1000 compound screening libraries for use in our development pipeline at no cost. These libraries have been screened in multiple assays to identify toxin inhibiting drugs Additional compounds have been provided for follow up studies and medicinal chemistry analyses.
Impact No outcomes as yet due to recent start date
Start Year 2019
 
Description Simple, affordable house ventilation for cooler, mosquito-free nights 
Organisation Durham University
Department School of Biological and Biomedical Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution The project is being led by PI Anne Wilson at LSTM.
Collaborator Contribution KADK are doing computational fluid dynamic modelling of different ventilation designs in housing. These innovative solutions will be pilot tested by teams at Durham University and MRC Gambia.
Impact Peer reviewed manuscript (doi: 10.1098/rsif.2022.0794)
Start Year 2019
 
Description Simple, affordable house ventilation for cooler, mosquito-free nights 
Organisation Medical Research Council (MRC)
Department MRC Unit, The Gambia
Country Gambia 
Sector Public 
PI Contribution The project is being led by PI Anne Wilson at LSTM.
Collaborator Contribution KADK are doing computational fluid dynamic modelling of different ventilation designs in housing. These innovative solutions will be pilot tested by teams at Durham University and MRC Gambia.
Impact Peer reviewed manuscript (doi: 10.1098/rsif.2022.0794)
Start Year 2019
 
Description Simple, affordable house ventilation for cooler, mosquito-free nights 
Organisation Royal Danish Academy of Fine Arts
Country Denmark 
Sector Academic/University 
PI Contribution The project is being led by PI Anne Wilson at LSTM.
Collaborator Contribution KADK are doing computational fluid dynamic modelling of different ventilation designs in housing. These innovative solutions will be pilot tested by teams at Durham University and MRC Gambia.
Impact Peer reviewed manuscript (doi: 10.1098/rsif.2022.0794)
Start Year 2019
 
Description Zebrafish biology and clinical respiratory medicine collaborations: Pulmonary arterial hypertension agents as adjunctive host-directed therapy for tuberculosis - a dual benefit of enhanced mycobacterial control and prevention of post-TB lung disease? 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Department Department of Immunology and Infection
Country United Kingdom 
Sector Academic/University 
PI Contribution Principal Investigator - using pilot data from my PhD I built the collaboration, sought the partners, led the application for funding and provided joint oversight of the experimental plans and data interpretation. Preliminary experimental data included in grant application to Tropical Infectious Diseases Consortium MRC Confidence in Concept : Pilot data suggesting a role for the prostacyclin axis in protective human mycobacterial immunity was gathered from my PhD. From the literature, the pathway is also differentially expressed following M. tuberculosis infection of primary macrophages from Vietnamese adults with latent TB infection, and prostacyclin metabolites are also enriched in the periphery of human granulomas. Prostacyclin is a biologically plausible host mediator as this vasoactive eicosanoid also modulates inflammation and acts upon both innate immune cells, including macrophages, neutrophils, Natural Killer cells, and adaptive T- and B-cells. We have shown functional relevance with enhanced mycobacterial killing in vitro using the clinical pulmonary hypertension drug treprostinil with human monocyte cell culture and Mycobacterium abscessus and potentially Mycobacterium tuberculosis.
Collaborator Contribution These research questions were planned through a combination of clinical and experimental approaches: Laboratory study Aim: To study the interaction between the prostacyclin pathway, mycobacterial infection, and vascular pathology in vivo using the zebrafish infection model. Together with Professor Mostowy research group, as a result of the Tropical Infectious Diseases Consortium Confidence in Concept funding as of September 2021 we have been able to test the hypothesis whether treprostinil would enhance mycobacterial killing in vivo using the zebrafish mycobacterial infection model. There was a dramatic host-mediated anti-mycobacterial effect for the intrinsicially drug resistant human pathogen Mycobacterium abscessus providing strong supportive data to further investigate a clinically relevant treatment in the face of global health challenges of antimicrobial resistance. Data from these experiments will be included in a manuscript that is in preparation for submission to a recognised high impact translational medicine journal. Outcomes: A postdoctoral research fellow was employed on the grant of which I was PI (MRC Confidence in Concept), whom I line managed. He introduced a new pathogen into the experimental repertoire of the Mostowy group (M Abscessus) and using pharmacological agonists and CRISPRant technology demonstrated the key receptor acted upon by an adjunctive therapy that enhances killing of intrinsically drug-resistant mycobacterium abscessus in an in vivo model. This data will go into an impactful publication and also provide the basis for future grant applications.
Impact Zebrafish infection model: https://themostowylab.org/
Start Year 2020
 
Description Zebrafish biology and clinical respiratory medicine collaborations: Pulmonary arterial hypertension agents as adjunctive host-directed therapy for tuberculosis - a dual benefit of enhanced mycobacterial control and prevention of post-TB lung disease? 
Organisation Wellcome Trust
Department Malawi-Liverpool Wellcome Trust Clinical Research Programme
Country Malawi 
Sector Academic/University 
PI Contribution Principal Investigator - using pilot data from my PhD I built the collaboration, sought the partners, led the application for funding and provided joint oversight of the experimental plans and data interpretation. Preliminary experimental data included in grant application to Tropical Infectious Diseases Consortium MRC Confidence in Concept : Pilot data suggesting a role for the prostacyclin axis in protective human mycobacterial immunity was gathered from my PhD. From the literature, the pathway is also differentially expressed following M. tuberculosis infection of primary macrophages from Vietnamese adults with latent TB infection, and prostacyclin metabolites are also enriched in the periphery of human granulomas. Prostacyclin is a biologically plausible host mediator as this vasoactive eicosanoid also modulates inflammation and acts upon both innate immune cells, including macrophages, neutrophils, Natural Killer cells, and adaptive T- and B-cells. We have shown functional relevance with enhanced mycobacterial killing in vitro using the clinical pulmonary hypertension drug treprostinil with human monocyte cell culture and Mycobacterium abscessus and potentially Mycobacterium tuberculosis.
Collaborator Contribution These research questions were planned through a combination of clinical and experimental approaches: Laboratory study Aim: To study the interaction between the prostacyclin pathway, mycobacterial infection, and vascular pathology in vivo using the zebrafish infection model. Together with Professor Mostowy research group, as a result of the Tropical Infectious Diseases Consortium Confidence in Concept funding as of September 2021 we have been able to test the hypothesis whether treprostinil would enhance mycobacterial killing in vivo using the zebrafish mycobacterial infection model. There was a dramatic host-mediated anti-mycobacterial effect for the intrinsicially drug resistant human pathogen Mycobacterium abscessus providing strong supportive data to further investigate a clinically relevant treatment in the face of global health challenges of antimicrobial resistance. Data from these experiments will be included in a manuscript that is in preparation for submission to a recognised high impact translational medicine journal. Outcomes: A postdoctoral research fellow was employed on the grant of which I was PI (MRC Confidence in Concept), whom I line managed. He introduced a new pathogen into the experimental repertoire of the Mostowy group (M Abscessus) and using pharmacological agonists and CRISPRant technology demonstrated the key receptor acted upon by an adjunctive therapy that enhances killing of intrinsically drug-resistant mycobacterium abscessus in an in vivo model. This data will go into an impactful publication and also provide the basis for future grant applications.
Impact Zebrafish infection model: https://themostowylab.org/
Start Year 2020
 
Title AZAQUINAZOLINE DERIVATIVES FOR USE IN TREATING OR PREVENTING DIROFILARIA INFECTION IN A MAMMAL 
Description Provided is a compound of formula (I), or pharmaceutically acceptable salt or solvate thereof, as defined herein for use in the treatment or prevention of a Dirofilaria infection in a mammal. The compounds are also for use in the treatment or prevention of diseases or conditions caused by a Dirofilaria infection in a mammal. Also described are corresponding methods of treating or preventing a Dirofilaria infection in a mammal. 
IP Reference WO2022152918 
Protection Patent / Patent application
Year Protection Granted 2022
Licensed No
Impact in discussion with Zoetis regarding potential outlicensing.
 
Title METHODS AND COMPOSITIONS FOR THE TREATMENT OF SNAKE BITE 
Description The disclosure herein are materials and methods for the treatment of snake bite. Aspects of the disclosure includes pharmaceutical compositions, and kits, both of which may be of use in the treatment of snake bite. 
IP Reference US2023054792 
Protection Patent / Patent application
Year Protection Granted 2023
Licensed No
Impact Patent application filed. Components of the drug combination that is the subject of the patent are moving forwards into clinical development.
 
Title use of prostanoid receptor modulators to treat nontuberculous mycobacterial infections 
Description a prostanoid receptor modulator for use in a method of treating or preventing a nontuberculous mycobacterial infection. Filed by Chariot Innovations Ltd at UK Intellectual Property Office on 28 September 2022. 
IP Reference 2214206.1 
Protection Patent / Patent application
Year Protection Granted
Licensed No
Impact Related data forms basis of recent and future grant applications, including where industry partnership is valued.
 
Description American Heartworm Society Triannual Congress 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Inivited talk and poster at the American Heartwom Society Congress, New Orleans
A large number of veterinarian practicioners and industry representatives were present.
NC3Rs funded research to develop alternative screening models and anti-Wolbachia drug research and development was presented and discussed.
Follow on invited review article was submitted to Veterinary Parasitology
Year(s) Of Engagement Activity 2019
URL https://www.heartwormsociety.org
 
Description British Society for Immunology Midlands Group University of Birmingham Immunology Seminar 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Seminar delivered on Filariasis lipids in Pathogenesis (FLiP) MRC Programme grant activities. Academics engaged with potential future knowledge exchange and collaborations discussed
Year(s) Of Engagement Activity 2024
URL https://www.birmingham.ac.uk/research/immunology-immunotherapy
 
Description Centre for Excellence in Infectious Disease Research Innovations Industry Symposium 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact On day meeting and networking session with national and international healthcare companies.
Oral presentation and poster presented
Discussed NC3Rs and MRC funded research to discover and develop next generation anti-Wolbachia drugs
Year(s) Of Engagement Activity 2020
URL https://www.lstmed.ac.uk/news-events/events/ceidr-innovations-industry-symposium-accelerating-soluti...
 
Description World NTD Day 2020 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact I organised and participated in the inaugural "World NTD Day" 2020 outreach event at Liverpool School of Tropical Medicine
The face to face audience engagement was internal to LSTM staff by way of a coffee morning with NTD outreach stands
This was followed by engagement to external audiences via live feed of a webinar and associated social and local print media
Year(s) Of Engagement Activity 2020
URL https://www.lstmed.ac.uk/news-events/seminars-and-lectures/world-ntd-day-seminar
 
Description invited speaker International Congress of Tropical Medicine and Malaria 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited presentation on the role of type-2 inflammation and bioactive lipids inducing lymphatic disease in filariasis
Year(s) Of Engagement Activity 2022
URL https://ictmm2020.org
 
Description presentation at USA Lymphatic Research forum 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Discussed opportunity of drug targeting bioactive lipids as a pharmacological lymphoedema therapy with USA lymphatic clinical and basic research audience. Audience engagement with follow up for more information and potential collaborations.
Year(s) Of Engagement Activity 2023
URL https://keck.usc.edu