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.
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.
Organisations
- Liverpool School of Tropical Medicine (Lead Research Organisation)
- DURHAM UNIVERSITY (Collaboration)
- Ministry of Health and Sports (Collaboration)
- Centre for Excellence in Infectious Disease Research Innovations (Collaboration)
- Wellcome Trust (Collaboration)
- London School of Hygiene and Tropical Medicine (LSHTM) (Collaboration)
- Johnson & Johnson (Collaboration)
- Medical Research Council (MRC) (Collaboration)
- UNIVERSITY OF LIVERPOOL (Collaboration)
- James Cook University (Collaboration)
- Royal Danish Academy of Fine Arts (Collaboration)
People |
ORCID iD |
Publications
Albulescu L
(2020)
A therapeutic combination of two small molecule toxin inhibitors provides broad preclinical efficacy against viper snakebite
in Nature Communications
Albulescu LO
(2020)
Preclinical validation of a repurposed metal chelator as an early-intervention therapeutic for hemotoxic snakebite.
in Science translational medicine
Carrasco-Tenezaca M
(2023)
Effect of passive and active ventilation on malaria mosquito house entry and human comfort: an experimental study in rural Gambia
in Journal of The Royal Society Interface
Clare RH
(2021)
Small Molecule Drug Discovery for Neglected Tropical Snakebite.
in Trends in pharmacological sciences
Hong W
(2023)
Transformation of the Manufacturing Process from Discovery to Kilogram Scale for AWZ1066S: A Highly Specific Anti- Wolbachia Drug Candidate for a Short-Course Treatment of Filariasis
in Organic Process Research & Development
Quek S
(2022)
Wolbachia depletion blocks transmission of lymphatic filariasis by preventing chitinase-dependent parasite exsheathment
in Proceedings of the National Academy of Sciences
Turner JD
(2020)
Novel anti-Wolbachia drugs, a new approach in the treatment and prevention of veterinary filariasis?
in Veterinary parasitology
Xie C
(2020)
Neutralizing Effects of Small Molecule Inhibitors and Metal Chelators on Coagulopathic Viperinae Snake Venom Toxins.
in Biomedicines
Xie C
(2020)
Varespladib Inhibits the Phospholipase A2 and Coagulopathic Activities of Venom Components from Hemotoxic Snakes.
in Biomedicines
Xie C
(2020)
Neutralising effects of small molecule toxin inhibitors on nanofractionated coagulopathic Crotalinae snake venoms
in Acta Pharmaceutica Sinica B
| 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 | Target Malaria - Phase II |
| Amount | $2,724,003 (USD) |
| Organisation | Imperial College London |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 10/2021 |
| 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 | 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 | Ongoing research - no outputs or outcomes |
| 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 | Ongoing research - no outputs or outcomes |
| 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 | Ongoing research - no outputs or outcomes |
| 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 | 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 | Part of grant application for £2,000,000 from LifeArc in their call for repurposing existing therapies and compounds as new treatments for chronic respiratory infection in bronchiectasis and cystic fibrosis, https://www.lifearc.org/strategy/respiratory-health/chronic-respiratory-infection-translational-challenge/ |
| 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 | 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 |