The MRC CiC Tropical Infectious Disease Consortium, is a partnership between leading UK institutes involved in translational research in tropical infectious diseases and includes the Centre for Drugs and Diagnostics (CDD) at the Liverpool School of Tropical Medicine, the London School of Hygiene and Tropical Medicine, the Jenner Institute at Oxford University and Public Health England Microbiology Services in Porton Down.
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The funded themes have so far included 10 drug/biologics discovery projects, 1 adjunct therapy project, 1 intervention (bed nets), 16 vaccines development projects (including an evaluation of a Zika virus fowlpox-based vaccine), 11 diagnostic discovery/development projects, 2 anti-venom, and 6 new insecticide resistance, surveillance and control tools. MRC CiC project funding has directly contributed to 6 patent applications and 1 trademark. Completed projects have gone on to lever over £9.5 million in additional external funding from a variety of sources including UKRC, Wellcome Trust, Bill & Melinda Gates Foundation and Industry.
The Consortium was successful in securing MRC funding for 2016-17 and a new call for projects will be made in Q2 2017.
The funding philosophy of the consortium will remain the same i.e. funding translational research based on potential medical impact and ‘developability’ and an ambition of significant acceleration in time to product delivery.
Current MRC CiC Awards (2018)
|
PI surname |
PI name |
PI institution |
Co-Is and institutions |
Title |
Synopsis |
Amt awarded |
|
Adams |
Emily |
Liverpool School of Tropical Medicine |
|
Flavivirus diagnostics – novel antibody detection systems to accurately diagnose and differentiate 15 flavivirus infections |
We propose to develop serological diagnostics to identify dengue, yellow fever, Zika, Japanese Encephalitis and eleven other high-priority flaviviruses. We will use antigen constructs, developed at LSTM for vaccine research, as receptors for antibody complexes using ELISA. We will further evaluate ELISAs with clinical samples from collaborators Public Health England. If successful we aim to further develop rapid diagnostic tests (RDTs) with our commercial partner Absolute Antibody. These diagnostic products have a huge potential commercial value, as current assays have poor specificity. The clinical management of patients, epidemiological data and upscale of interventions could be vastly improved by accurate serological tests. |
£45,873.60 |
|
Dowall |
Stuart |
Public Health England,
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Roger Hewson (PHE) |
Generation of a source of positive antibody controls for development of an ELISA diagnostic test for Crimean-Congo Haemorrhagic Fever virus. |
Crimean-Congo Haemorrhagic Fever virus (CCHFV) is a highly contagious pathogen responsible for severe disease. It is primarily transmitted to humans by ticks. The viremic period is brief making its direct detection by PCR of limited value as patients may present after virus has been cleared. Thus diagnosis also relies on serological assays to detect specific CCHFV antibodies. PHE have developed an ELISA based on recombinant CCHFV nucleoprotein. Whilst patient material has been used to assess assay performance, a standardised antibody preparation is needed to allow the assay to be developed into a commercial and CE-marked test. |
£47,789.97
|
|
Milicic |
Anita |
University of Oxford, Jenner Institute, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ |
Prof. Eleanor Stride, Dept. of Engineering, University of Oxford |
Single administration of prime-boost malaria vaccine enabled by engineering advancements in precise vaccine encapsulation methods |
The concept of single administration vaccines using biodegradable microspheres, containing vaccine booster doses for delayed in vivo release, has been a strategic priority of the WHO since 1990s but has so far eluded vaccine developers.
Conventional techniques used to prepare delayed release microspheres have been ineffective because of damage to the vaccine antigen during preparation or irreproducibility of release kinetics.
The novelty of this proposal is in building on the state of the art technological methods for microcapsule production which are readily accessible to us at Oxford, and which we have shown enable to maintain vaccine viability and stability post-encapsulation. |
£47,645.88 |
|
Pleass |
Richard |
Liverpool School of Tropical Medicine Pembroke Place Liverpool L3 5QA UK |
Professor Alain Kohl – MRC University of Glasgow Centre for Virus Research, Professor Roger Hewson - Porton Down |
Hypersialylated blockers of Zika virus (ZIKV) infectivity and neuropathology |
Zika virus (ZIKV) is a mosquito-borne human pathogen of the Flaviridae family, which includes dengue virus (DENV), West Nile virus (WNV) and Japanese encephalitis virus (JEV). ZIKV infection has been linked to severe neurological disorders including Guillain-Barré syndrome (GBS), which is currently treated with intravenous immunoglobulin (IVIG). With our CiC1 award we developed, patented and are licensing to Pharma, recombinant IVIG mimetics with remarkable properties, including 100-fold enhanced efficacy over IVIG in the treatment of autoimmune diseases. We intend to test if these novel compounds can control ZIKV infectivity in neural systems and demyelination. |
£47,789.97 |
|
Pulido-Gomez |
David |
University of Oxford, Jenner Institute, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ |
Prof Simon J Draper (Jenner Institute, University of Oxford) |
Development of a new virus-like particle (VLP) invasion protein complex vaccine for blood-stage Plasmodium falciparum malaria |
|
£37,993.39 |
|
Roberts |
Adam |
Liverpool School of Tropical Medicine |
W. David Hong (University of Liverpool), Paul M. O’Neill (University of Liverpool) and Victoria Savage (AMR Centre Ltd.) |
Determining the potency of hybrid antibiotics, informed by collateral sensitivity networks, against a panel of susceptible and resistant clinical Escherichia coli isolates |
We urgently need to develop novel antimicrobials as resistance is now a serious global issue. We recently demonstrated reproducible collateral-sensitivity (CS) networks in Escherichia coli. CS occurs when sensitivity to one drug increases upon the development of resistance to another drug. Hybridisation of two antibiotics can lead to increased therapeutic efficacy; however, the choice of antibiotics has never been informed by CS. This project aims to investigate novel hybrid (fluoroquinolone and aminoglycoside) antibiotics against E. coli, and determine if CS between these two classes of antibiotics will lead to a reduction in resistance development and persistence through a hybridisation strategy. |
£47,462.13 |
|
Van Bocxlaer |
Katrien |
London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, United Kingdom |
Simon Croft (LSHTM) Andy Harris (Pharmidex) Charles Mowbray (DNDi) |
Film-forming systems for sustained drug delivery to treat cutaneous leishmaniasis |
Topical treatment of skin diseases is desirable because i) the drug product is applied directly to the affected site, achieving high drug levels locally with limited systemic exposure and associated side effects, and ii) it is easy to apply increasing patient compliance. This project will focus on the exploration of polymeric film-forming systems (FFSs) as topical drug delivery system for pre-clinical candidate drugs for cutaneous leishmaniasis (CL). FFSs facilitates drug delivery by increasing the contact time and/ or maintaining the delivery of the drug to the local site of action by forming a drug reservoir in or on the skin. |
£47,789.97 |
|
Acosta-Serrano |
Alvaro |
Liverpool School of Tropical Medicine |
Dr. Mark Paine (VBD-LSTM); Dr Rosemary Lees and Helen Williams (LITE-LSTM); Prof Pedro Oliveira (UFRJ, Brazil); Matthew Rogers (LSTMH) |
Controlling malaria transmission using environmentally ‘friendly’ sugar baits |
Blood feeding insects (BFI) are vectors of the most prevalent diseases, with a worldwide disease incidence of over 1 billion cases and more than 1 million deaths annually. Control of BFI typically involves the use of neurotoxic insecticides like organophosphates and pyrethroids. Furthermore, the spread of insecticide-resistance in vector populations demands development of novel approaches to block transmission of vector-borne diseases (VBD). In this project, we aim to continue evaluating the suitability of Nitisinone, a tyrosine metabolism inhibitor, in Attractive Targeted Sugar Baits (ATSB). |
£28625.24 |
|
Urban |
Britta |
Liverpool School of Tropical Medicine |
Richard Pleass, LSTM |
Reverse antibody engineering for delivery of therapeutic antibodies against severe malaria |
The pathology of severe malaria is largely due to adhesion of infected erythrocytes to endothelial cell protein C receptor (EPCR). The PfEMP1 protein binding to EPCR is highly variant with an EPCR- binding site that is heterogenous in sequence but biochemically conserved. We recently isolated and expressed recombinant human antibodies that cross-react with a diverse range of EPCR-binding PfEMP1 using single B cell analysis. We now propose to explore these antibodies for development of adhesion-blocking adjunct therapy of severe malaria through molecular engineering of their Fc region to increase their avidity and effector function, ready for testing in pre-clinical trial. |
£46311.35 |
|
Gilbert |
Sarah |
University of Oxford, Jenner Institute, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ |
Dr. Teresa Lambe, University of Oxford, Dr. Stuart Dowall, Public Health England, Dr. Sue Charlton, Public Health England, Dr. Dalan Bailey, The Pirbright Institute |
Development of a vaccine to prevent Crimean-Congo haemorrhagic fever virus mediated disease |
Crimean-Congo haemorrhagic fever (CCHF) is the most widespread tick-borne viral disease affecting humans and is associated with case fatalities of ≥30% during outbreaks. CCHFV is endemic in many regions, including Africa, and it is widely accepted that cases are under-reported due to limited resources. There is an unmet need for the development of efficacious vaccines against viral haemorrhagic fever caused by CCHFV. We aim to deliver a single dose, highly effective vaccine solution through the work described herein. |
£47786.83 |
|
Harrison |
Rob |
Liverpool School of Tropical Medicine |
Stuart Ainsworth, Nicholas Casewell, Richard Pleass (all LSTM) |
Novel immunising tools to generate high avidity, cross-generic IgGs to substantially improve treatment of snake venom-induced neurotoxicity throughout sub-Saharan Africa |
Neurotoxicity is the most rapidly lethal pathology of snake envenoming. Because the sub-12kDa venom neurotoxins are notoriously weak immunogens and molecularly diverse, treatment currently requires 5-15 vials of antivenom IgG, which cause delay, severe adverse effects and is frequently unaffordable to patients and rural hospitals.
Focussing on African venom neurotoxins we will: Overcome molecular diversity: by deploying our proven bioinformatics-designed epitope-string-immunogen (ESI) approach to generate IgGs that cross-generically bind and neutralise the functions of PhospholipasesA2 neurotoxins.
Overcome weak immunogenicity: by using the uniquely-antigenic properties of Virus-Like-Particles or Immune-Complex-Mimetics to immunise sheep (antivenom-manufacturing animals) with these novel ESIs and multi-3FingerToxin antigen constructs. |
£ 47789.97 |
|
Ward |
Stephen |
Liverpool School of Tropical Medicine |
Prof M. Taylor (LSTM), Dr J. Turner (LSTM), Prof P. O’Neill (University of Liverpool), Dr D. Hong (University of Liverpool) and Dr Fabian Gusovsky (Eisai Inc.) |
Development of a back-up molecules for the anti-Wolbachia macrofilaricidal pre-clinical candidate AWZ1066S |
The anti-Wolbachia macrofilaricide candidate AWZ1066S is undergoing formal pre-clinical development in preparation for first-into-human trials. It is critically important and industry standard practice to develop back-up compounds to mitigate any potential issues identified during pre-clinical and clinical development. The A∙WOL discovery programme initiative developed analogues of AWZ1066S late in the programme that have superior qualities to the current candidate in terms of anti-Wolbachia activity in vitro and in vivo and time to kill dynamics. If successful, the data generated in this project will formalise the selection of a quality back-up candidate to AWZ1066S |
£ 49658.56 |
|
Biagini |
Giancarlo |
Liverpool School of Tropical Medicine |
Prof P. M. O’Neill (UoL), Dr W. D. Hong (UoL), Dr G. Nixon (UoL), R. B. Abramovitch (Michigan State University), Dr Joanna Bacon (Porton Down) and Dr Anna Upton (TB Alliance) |
Endoperoxide containing hybrid anti-tuberculosis agents to tackle latent Mycobacterium tuberculosis |
The DosRST system in mycobacterium tuberculosis (Mtb) plays a critical role in the survival of the bacteria during non-replicating persistence (NRP). The co-investigators have identified several endoperoxide-based scaffolds that can target the DosRST pathway to resensitise NRP Mtb to anti-tuberculosis agents; these small molecules have low inherent activity versus latent Mtb as single drugs. In this project, we proposed to hybridise our endoperoxide scaffolds with known nanomolar potent MmpL3 inhibitors to tackle latent Mtb. The proof-of-concept data from this project can open up a new approach to anti-TB drug design and will form the basis of a full drug discovery programme. |
£ 47483.16 |
Previous MRC CiC Awards:
PI Surname & Institution |
Co-Is & Institutions |
Title |
Synopsis |
Amount awarded |
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2013/14 |
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Emily Adams Liverpool School of Tropical Medicine |
Luis Cuevas (LSTM), Matthew Walls (Epistem), Peter Foster (Epistem)
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Integrated diagnosis of TB and HIV using Genedrive® technology |
Our aim is to develop an integrated cartridge based on Epistem’s Genedrive® technology for the simultaneous diagnosis of Tuberculosis and HIV, including TB drug resistance markers, which is suitable for use at the point of care.
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£46,260.00
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Giancarlo Biagini Liverpool School of Tropical Medicine
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Stephen Ward (LSTM), Neil Berry (UoL), Paul O’Neill (UoL) and Ann Rawkins (PHE, Porton Down) |
Identification of Early Antitubercular Leads using Syngenta assets
|
A 100,000-diverse small molecule library is presently being screened against Mycobacterium tuberculosis (MtB) in the Cat3 laboratories at LSTM. The current funding will only allow for hit confirmation (IC50) against replicating (RP) Mtb in liquid culture (assessed by almar blue 5-day assay). In this MRC CiC proposal we wish to take tractable hits to generate early leads with a data package that would allow for follow-on funding (TBA, MRC DPFS, Wellcome Trust). The Co-Is are involved in a number of TB drug discovery projects (e.g. MRC DPFS) and TB drug consortiums (e.g. IMI TB Predict) and through this experience and in discussions with the TBA (TB Alliance) have identified an accelerated route to lead identification. The Lead Identification (LI) pathway includes; (i) chemoinformatics to remove non-tractable hits, (ii) in house Wayne model to select RP and non-replicative (NRP) Mtb active compounds, (iii) Time-kill assays to identify bactericidal inhibitors, (iv) determination of microsomal stability of compounds to measure in vitro intrinsic clearance (or to identify metabolites formed), (v) Synthesis of prioritised leads and (vi) in vivo testing and preliminary in vivo DMPK. |
£46,750.00
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Simon Croft London School of Hygiene and Tropical Medicine |
Elaine Warburton (QuantuMDx), Prof Sanjeev Krishna and Dr Henry Staines (both St George’s, University of London)
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Development of a Leishmania identification PCR assay for use with next generation PoC diagnostic devices |
The project aims to provide proof of principle for an accurate, rapid and cheap PCR-based point-of-care diagnostic assay for kinetoplastids. This will be achieved by developing a simple Leishmania diagnostic assay that will be ported directly onto a novel point-of-care diagnostic device developed to diagnose and provide resistance status for malaria. |
£44,880.00 |
|
Alexander Douglas The Jenner Institute, University of Oxford |
Professor Adrian Hill, DPhil FRCP, Jenner Institute, University of Oxford, Collaborator: Erik Jans, Maxcyte Inc |
Test many, test quickly, test cheaply- accelerating clinical proof-of-principle for novel vaccines using flow-electroporation-mediated transient transfection of mammalian cells for GMP antigen production. |
Production of clinical-grade antigen to Good Manufacturing Practice (GMP) standards is expensive and time-consuming and represents a critical bottleneck in the protein subunit vaccine development pipeline. This project proposes to adapt for use in the vaccine field a proven flow electroporation technology which has been in use for over a decade in the pharmaceutical industry for GMP cell-therapy and small-scale monoclonal antibody production. This has the potential to facilitate clinical translation of future candidate vaccine antigens by dramatically reducing the cost and increasing the throughput of GMP manufacture. |
£46,285.00 |
|
Simon Draper The Jenner Institute, University of Oxford |
Dr Jack Eby (Vedantra Pharmaceuticals) – External / Industrial Collaborator] |
Improving the Longevity of Vaccine-Induced Antibody Responses against the Blood-Stage Plasmodium falciparum Malaria Parasite |
Significant challenge for vaccine immunologists is to better understand how to achieve the induction and maintenance of high level protective antibody titres. A novel vaccine delivery platform based on interbilayer-crosslinked multilamellar vesicles (ICMVs) has shown a remarkable ability to lead to high and sustained antibody responses without waning over time. We now wish to assess this system for proof-of-concept using a clinical-grade PfRH5 protein vaccine which has been shown to induce broadly-neutralising antibodies against the blood-stage malaria parasite. |
£46,750.00 |
|
Philip McCall Liverpool School of Tropical Medicine |
Prof David Towers, Dr Cathy Towers (School of Engineering (Uni Warwick), Dr Fabian Mashauri (NIMR, Mwanza, Tanzania) |
Novel bednet designs to improve insecticide-treated net efficacy and combat insecticide resistance |
Insecticide treated bednets (LLINs) are essential tools for malaria prevention but their future is threatened by resistance to pyrethroids, the only insecticides permitted on bednets. Using state-of-the-art video-tracking systems, our unique research team of vector biologists and optical engineers has gained extraordinary insight into host seeking behaviour of the major African malaria vector Anopheles gambiae at human-occupied LLINs. Exploiting these newly revealed behaviours we have devised novel LLINs designed to target mosquitoes, while minimising risk of human contact, with a range of insecticidal formulations. In the proposed project, this team will deliver evidence to demonstrate: (1) that An. gambiae will come into contact with the new LLINs, as designs intended; (2) that lethal doses of insecticide can be delivered during those contacts; (3) that pyrethroid-resistant An. gambiae can be killed in this way. The project will involve analysis of video-tracked behaviour and bioassay of mosquitoes, in purpose-built insectary at Liverpool and an experimental field hut in Tanzania. |
£46,745.00 |
|
Anita Milicic The Jenner Institute, University of Oxford |
Helen Fletcher (LSHTM), Helen McShane,The Jenner Institute (Uni of Oxford) |
Novel vaccine encapsulation technology for a single dose prime-boost immunisation against TB |
We plan to develop a novel vaccine technology that would enable conversion of prime-boost vaccines into a single dose immunisation, where the boost vaccine is encapsulated for delayed release in vivo, admixed with the priming vaccine and delivered as a single injection. As a proof of concept, we propose to address vaccination against tuberculosis (TB), a major tropical disease threat. Following the optimisation of microcapsule synthesis with a model protein, we will encapsulate the major Mycobacterium tuberculosis (Mtb) secreted protein, Ag85A together with an adjuvant. We will test the delayed release technology by immunising mice with a mixture of BCG and encapsulated adjuvanted Ag85A, and assessing immunogenicity and protective efficacy against TB. To explore this approach further, we will modify the system to administer encapsulated chimpanzee adenoviral (ChAd) vector encoding Ag85A (ChAd-85A) as the boost vaccine, based on our recent pre-clinical observations of high efficacy against TB following a BCG prime, ChAd- 85A boost regimen. The use of this type of microencapsulation would benefit any prime-boost vaccine but could also be adapted to vaccines that require multiple doses for efficacy. The design and composition of the capsules would determine the period of capsule dormancy in vivo, prior to the release of the vaccine, and could be tailored to different vaccines’ prime-boost intervals. Reducing the number of administrations would simplify vaccine deployment by reducing costs and increasing uptake rates. Success in the proposed work would make a strong case for future clinical testing. |
£46,750.00 |
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Mark Paine Liverpool School of Tropical Medicine |
Mark Rowland – Head, Department of Disease Control (LSHTM), Hanafy Ismail –Vector Biology (LSTM), Paul Millner – Professor of Bionanotechnology and Head of School of Biomedical Science (Leeds Uni), Paul O’Neill – Chemistry Dept (Uni of Liverpool) |
Development of Adhiron based insecticide monitoring tools
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Our objective is to develop a set of novel Adhirons that can bind DDT with high specificity. By producing DDT-Haptens and screening them against the Adhiron library we will be able to produce a simple ELISA based assay that can be benchmarked against our current DDT IQK and HPLC in field operations in India. This will establish the base-line data necessary to move forward and expand the insecticide range and engage with industry for commercialisation. The latter is facilitated as we (MP) have an existing commercialisation pipeline of insecticide quantification kits via the Indian Wellcome Trust Translation programme and IVCC partners. |
£27,955.00 |
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Ann Rawkins Public Health England, Porton Down
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Prof. Helen McShane (Co-investigator, Jenner Institute, University of Oxford), Dr. Christopher Woelk (Co-investigator, University of Southampton) |
Evaluation of new antigens for subunit vaccines against Mycobacterium tuberculosis. |
This project will evaluate the immunogenicity of TB vaccine candidates previously predicted by a sophisticated reverse vaccinology approach in order to facilitate the formulation of new subunit vaccines against Mycobacterium tuberculosis. |
£40,000.00
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Britta Urban Liverpool School of Tropical Medicine |
Alister Craig(LSTM), Richard Pleass(LSTM) and Simon Draper (Jenner Institute) |
Isolation of human monoclonal antibodies that reverse adhesion of Plasmodium falciparum infected erythrocytes to ICAM-1 |
Adhesion of Plasmodium falciparum Infected erythrocytes to ICAM--‐ 1 is central for the pathology of severe cerebral malaria. We propose to produce recombinant human monoclonal antibodies, which can block or reverse adhesion of infected erythrocytes to ICAM--‐1. |
£46,750.00 |
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Steve Ward Liverpool School of Tropical Medicine |
Giancarlo Biagini (LSTM), Neil Berry (UoL), Paul O’Neill (UoL) |
Identification of Early Antimalarial Leads using Syngenta assets |
A 100,000-diverse small molecule library from Syngenta is presently being screened at LSTM. A quarter of the compounds have thus far been screened with 0.1% of the compounds displaying an IC50 < 1uM. Current funding will only support the screening activity and in this MRC CiC we wish to request for further investment to support hit-to-lead activities. Using an accelerated pathway to lead identification, we will use (i) Chemoinformatics to remove non-tractable compounds or those containing metabolic alerts, (ii) in house high content imaging to find ring/fast killers, (iii) a luciferase-based viability assay (in collaboration with Dr Paul Horrocks, Keele University) to confirm inhibitor parasite reduction rates, (iv) microsomal stability testing to predict intrinsic clearance, (v) chemical synthesis for small scale up of early leads and (vi) in vivo testing with concurrent DMPK (P. berghei rodent model). We anticipate that molecules occupying novel chemical space that progress to early leads displaying fast killing kinetics will be competitive for follow-on support in lead optimisation studies. |
£41,700.00 |
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2014/15 |
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David Baker London School of Hygiene and Tropical Medicine |
Mark Gardner, Andy Bell, Tanya Parkinson (Salvensis); Alan Brown (Pfizer); Giancarlo Biagini (LSTM) |
Investigation of Pfizer & public domain cyclic nucleotide phosphodiesterase (PDE) inhibitors as possible antimalarial drugs that treat disease and block transmission |
We aim to identify anti-malarial chemotypes which act through inhibition of PfPDEs with potential for good PK. We have demonstrated potent Pfal blood stage growth inhibition with good evidence of on-target activity using a small panel of Pfizer hPDE inhibitors. PK of the compounds tested so far is poor. Here we will examine a broad spectrum of hPDE hemotypes from Pfizer and the literature for potency against the parasite, on target activity, non-cytotoxicity and good PK. Success will lead to a compound good enough to demonstrate activity in the SCID mouse or a chemistry program to deliver such an agent. |
£46,750 |
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Giancarlo Biagini Liverpool School of Tropical Medicine |
David Baker (LSHTM), Stephen Ward (LSTM), Paul O’Neill (University of Liverpool/ School of Tropical Medicine), Mark Wenlock (AstraZeneca, Alderley Edge), Raman Sharma (LSTM) |
Towards the generation of safe 8-aminoquinolines: Development of Quantitative structure activity/quantitative structure property (QSAR/QSPR) relationships of primaquine analogs to accurately predict redox potentials |
Despite its development some 60 years ago, the mode of action of primaquine, the only drug proven to be clinically effective against liver and sexual stage human malaria parasites, is unknown. This knowledge gap is a major barrier to the development of safer alternative therapies based on rational redesign of molecules that share this mechanism of action. We have new data demonstrating that hydroxylated primaquine metabolites are redox cycled in vitro by P. falciparum ferredoxin-NADP+ reductase (PfFNR). Significantly, this data is the first demonstration of specific parasite enzymes involved in the mode of action of the 8-aminoquinolines and represents a starting point for drug discovery. In this project, we aim to develop Quantitative structure activity/quantitative structure property (QSAR/QSPR) relationships allowing the prediction of redox potentials. This information will form the foundation for future rational drug redesign strategies aimed at delivering the next generation of transmission blocking/radical curative antimalarials with utility for the malaria elimination agenda |
£40,200 |
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Simon Croft London School of Hygiene and Tropical Medicine
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Dr Kelly S. Davidge, Dr J. Malcolm Wilkinson (Kirkstall Ltd, UK); Dr Mo Alavijeh (Pharmidex, UK); Dr Abhishek Ananthanarayan (InVitroCue, Singapore); Dr Emily Adams (LSTM)) |
Development of 2D and 3D in vitro dynamic/flow infection models for drug evaluation against Leishmania |
This project will focus on the development of 2D and 3D dynamic/flow infected culture models, with multi-time points, to measure the activity of novel compounds against Leishmania. Current anti-protozoal in vitro assays for determining the selective activity of novel chemical entities are based on static cultures with a single time point reading and more predictive models of infection are required for translation to in vivo activities in rodent models. |
£39,350 |
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Luis Cuevas Liverpool School of Tropical Medicine |
Dr. Emily Adams (LSTM) Dr. Thomas Edwards (LSTM) Dr. Jane Theaker (Qiagen, UK) |
Design and development of commercial multiplex qPCR and isothermal assays fit for chikungunya and dengue virus diagnosis, surveillance and dengue vaccine evaluation. |
We aim to develop an rt-qPCR CE marked diagnostic for the differentiation of chikungunya virus and the four main dengue virus serotypes for surveillance and a prototype near-patient test for differentiation of Chikungunya and dengue. Improved diagnostics are required to facilitate patient management, improved surveillance and to monitor the efficacy of future dengue vaccines. The assays will be co-developed as commercial products by LSTM and Qiagen In Vitro Diagnostics (Manchester. The tests will be evaluated in Ecuador and Brazil. |
£41,700 |
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Nicholas Feasey Liverpool School of Tropical Medicine |
David Cook (Blueberry Therapeutics Ltd); Christopher Parry (LSHTM); Giancarlo Biagini (LSTM) |
Formulation of ceftriaxone into nanoparticles to improve intracellular penetration and hasten intracellular killing of Salmonellae
|
Typhoid fever is responsible for an estimated 225,000 deaths/year. Resistance to standard antimicrobials is commonly seen, making ceftriaxone the first-line agent in many settings, however ceftriaxone penetrates the intracellular compartment more slowly than ciprofloxacin and is associated with prolonged fever clearance times and high relapse rates. Formulation of ceftriaxone into nanoparticles offers the potential to enhance intracellular delivery, thus improving its efficacy. Preliminary data has demonstrated we can formulate ceftriaxone into nanoparticles without reducing in-vitro activity. We propose to evaluate nano-formulations of ceftriaxone against standard ceftriaxone using the Operetta High Content Imaging System to determine intracellular clearance of S. Typhi. |
£43,950
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Roger Hewson Public Health England, Porton Down |
Dr Stuart Dowall (PHE); Prof Miles Carroll (PHE); Dr Alison Turner (The Jenner Institute) |
Redevelopment of a promising vaccine candidate for Crimean-Congo Haemorrhagic Fever virus (CCHFv) into a markerless MVA vector suitable for commercial development
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Scientists at Public Health England have constructed an experimental vaccine against Crimean-Congo Haemorrhagic Fever virus (CCHFv) by insertion of the glycoprotein-encoding region into a recombinant modified Vaccinia Ankara (MVA) viral vector. The vaccine has been shown to confer protection against an otherwise lethal challenge dose of virus in a susceptible mouse strain (type-I interferon receptor deficient), the accepted CCHF animal model. Immunogenicity results have shown the vaccine induces both cellular and humoral arms of the immune response. Recent passive and adoptive transfer studies have indicated that both T-cell and antibody-mediated immunity is required to exert any protective effects. The vaccine construct is currently a research-grade construct, containing regions encoding green-fluorescent protein (GFP), tissue plasminogen activator (tPA) and a V5-tag. To make the vaccine more suitable for commercialisation and clinical trials, a markerless MVA vector would be required. Therein, this project will transfer the CCHFv glycoprotein into a markerless MVA platform and compare immunogenicity and efficacy with the novel construct versus the existing vaccine candidate. |
£31,800
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Mark Paine Liverpool School of Tropical Medicine |
Mark Rowland (LSHTM); Manas Sarkar (Godrej); Ben Cobb (Epistem); David Weetman (LSTM); Emily Adams (LSTM); Hilary Ranson (LSTM) |
Field Diagnostic Kits for Insecticide Resistance |
Our aim is to develop ‘point of care’ systems for the screening of insecticide resistance markers in tropical disease transmitting insects in the field. |
£29,900 |
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Lisa Reimer Liverpool School of Tropical Medicine |
Bruce Alexander (Xeroshield); Nana-Kwadwo Britwum (Ghana Health Services); Darren Cook (LSTM), Emily Adams (LSTM) |
VESS: Vector excreta surveillance system for lymphatic filariasis |
We propose the development of a tool to collect, concentrate and filter wild mosquito excreta for the purpose of filarial DNA detection. The vector excreta surveillance system (VESS) is a xenomonitoring tool that directly responds to the emerging need of lymphatic filariasis (LF) elimination programmes to sensitively detect LF resurgence. Our preliminary work has shown that wild mosquitoes exploit artificial sugar sources and resting sites, and that filarial DNA can be recovered from mosquito excreta at least five days’ post-exposure to an infected bloodmeal. This proposal enables the development of this approach into a field-testable prototype through stakeholder consultation. |
£43,600 |
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Arturo Reyes-Sandoval The Jenner Institute, Oxford University |
Prof John Professor John M. Kelly (LSHTM) |
Pre-clinical protective efficacy of novel Chagas vaccine candidates: A final step towards clinical application. |
Chagas disease, caused by Trypanosoma cruzi remains a neglected tropical disease in the Americas, affecting approximately 7.5 million people. An efficacious vaccine would be a major, cost-effective approach to improving public health in the Americas. Two leading Chagas vaccine antigens (Tc24, TSA-1) have been used to develop MVA and adenoviral vectored vaccines at the Jenner Institute. The vaccine candidates induced outstanding immunogenicity in mice and we are joining efforts with LSHTM scientists to assess protective efficacy using novel transgenic parasites developed in this institution. Efficacy demonstration will be key for translation to a clinical trial supported by the MRC-DPFS scheme. |
£46,750 |
|
Jamie Rylance Liverpool School of Tropical Medicine |
Ben Morton, Daniela Ferreira, Jesus Reine (all LSTM) |
The whole blood phagocytosis assay: a near patient test to promote a personalised approach to immunomodulatory therapy. |
We wish to investigate a novel; clinically relevant ex vivo assay that utilises P4 peptide to measure phagocytic activity in patients with severe infection. We have developed the current assay using Liverpool Health Partners funding and will now prospectively validate our promising preliminary data in patients admitted to the hospital with infection. This project will generate data to support an application for NIHR i4i funding to commercialise the assay. We have previous successful experience of translating CiC funding in to DPFS award using the therapeutic rather than diagnostic limb of the P4 programme. |
£42,500 |
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Ahmed Salman The Jenner Institute, Oxford University
|
Florian Brod (Jenner Institute); Prof Chris J. Janse and Dr Shahid Khan (Leiden University Medical Centre); Prof Adrian V. S. Hill (Jenner Institute) |
Evaluation of Plasmodium falciparum SPECT-1 as a novel pre-erythrocytic vaccine candidate |
The most advanced malaria vaccine is RTS,S/AS01, based on the circumsporozoite protein (PfCSP). Using new transgenic parasite technology, we have recently screened 15 P. falciparum pre-erythrocytic antigens for their ability to protect against antigen-matched transgenic P. berghei parasites and identified a sporozoite antigen, PfSPECT-1 which induces high level efficacy mediated by antibodies. PfSPECT-1 is more protective in mice than PfCSP, which has been the leading sporozoite vaccine antigen for decades. We will compare the immunogenicity and efficacy of PfSPECT-1 as a vaccine candidate in several forms, particularly as virus-like particles in adjuvant, aiming to provide a promising new vaccine candidate. |
£46,750 |
|
George Warimwe The Jenner Institute, Oxford University |
Prof Sarah Gilbert (Jenner Institute); Prof Musaad Al-dubaib (Qassim University)
|
A One Health approach to MERS-CoV vaccines for camels and humans
|
Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging zoonosis that is highly prevalent in camels and causes life-threatening respiratory disease in humans. No licensed camel or human vaccines are currently available for MERS-CoV. Here, utilising a chimpanzee adenovirus platform with an established safety profile in camels and humans, we will develop a MERS-CoV vaccine for deployment in both these species. We aim to demonstrate induction of high titre neutralizing antibody and protective efficacy against experimental MERS-CoV challenge in camels, thus providing proof-of-concept for further development of a deployable product for use in camels and in subsequent human clinical trials. |
£46,750
|
2015/16 |
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Emily Adams Liverpool School of Tropical Medicine |
Dr. Thomas Edwards (LSTM) |
The development of a multiplex assay, using the Biogene QuRapid direct PCR system, for the detection of antimicrobial resistance markers and bacterial identification in Gram-negative sepsis |
We aim to develop a High Resolution Melt (HRM) assay capable of the detection of common sepsis causing bacteria, and identification of antimicrobial resistance markers, including ESBL and AmpC production, and CAT genes, in a single tube.
|
£44,735 |
|
Amaya Bustinduy London School of Hygiene and Tropical Medicine |
Prof. Michael Miles, LSHTM. Prof. Russell Stothard, LSTM. Prof. Steve Allen, LSTM. |
Development and application of a Recombinase Polymerase Amplification (RPA) point-of-care test for the detection of Giardiasis in resource limited settings. |
Giardiasis is a significant gastro-intestinal disease caused by Giardia lamblia with over 50 million children infected annually. In tropical regions, giardiasis is much under-reported as access to current point-of-care (POC) tests is limited and the available faecal-antigen tests have much lower sensitivity than real-time PCR assays, the diagnostic ‘gold standard’. With advances in isothermal DNA amplification technology, we intend to refine and adapt a novel field-appropriate, POC test based on recombinase polymerase amplification (RPA) useful in resource-poor settings and able to differentiate infection intensities. Validated on laboratory reference material, an external evaluation will be undertaken in a prospective cross-sectional survey in Uganda. |
£47,339 |
|
Miles Carroll Public Health England, Porton Down |
Simon Funnell, Roger Hewson, Stuart Dowall and Julia Vipond. |
Evaluation of a Zika virus fowlpox-based vaccine construct in a murine model of infection |
This project is intended to evaluate the protective efficacy of a fowlpox-based vaccine based on addition of important conserved antigens present on the Zika virus. The antigen set will be common to those used in other candidate vaccine modalities with the benefit of greater freedom to pursue commercialisation of the candidate vaccine. PHE has developed a murine model of infection which is essential to evaluate this and other candidate vaccines. |
£47,829 |
|
Nicholas Casewell Liverpool School of Tropical Medicine |
Dr. Robert A. Harrison (LSTM) |
Rational design of a global, pathology-specific antivenom to treat lethal, snake venom-induced haemorrhage. |
Antivenoms for treating snakebite have, because of current manufacturing protocols, limited cross-species neutralising efficacy, weak specificity and poor safety profiles. We seek to address these deficiencies by generating a first-of-its-kind “pathology-specific” antivenom. Using the haemorrhagic snake venom metalloproteinases as our target, we will use phage display to identify cross-species conserved epitopes as immunogens, and test the efficacy of IgG from the immunogen-immunised mice to neutralise venom-induced haemorrhage in vitro and in vivo. The outputs from this proof-of-principle study will springboard the development of a novel antivenom with global efficacy against venom-induced haemorrhage – the most frequently lethal pathology of snake envenoming. |
£47,682 |
|
Michael Coleman Liverpool School of Tropical Medicine |
Knut Staring (University of Oslo) |
Towards the next generation of Disease Surveillance Systems. |
Currently, two main solutions for managing disease control programmes in Africa and Asia exist, the Disease Data Management System and the District Health Information System. Both have complementary functionality: the DDMS supports operational decision-making, including disease outbreak detection, entomology, and intervention monitoring. The DHIS2 possesses a strong community of health users. Creating a consolidated analytical platform combining the functionality of both systems will have a transformative impact on the way data is used as an intervention. We expect that such a system would greatly increase the availability of data for use in decision-making in current (malaria) and novel (Zika) programs. |
£48,239 |
|
Adrian Hill Jenner Institute, University of Oxford |
Prof. Zhanfeng Cui, Professor of chemical engineering
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Development of a novel biocompatible matrix for sugar membrane technology for thermostability of an adjuvanted malaria vaccine.
|
The sugar-membrane technology currently being advanced at the Jenner Institute has been shown to improve thermostability of a wide range of vaccines including polio, measles, liposome and alum adjuvanted subunit vaccines, and viral vectored vaccines. One of the two key components of the technology, the fibrous membranes come with a disadvantage of potential fibre shedding and difficulty in GMP standard manufacture. We have identified biocompatible polymers to replace existing matrix. The project aims to produce and test thermostability of an adjuvanted vaccine for malaria on a novel biocompatible GMP manufacturable matrix. |
£48,239
|
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Jing Jin Jenner Institute, University of Oxford |
Prof Simon J Draper (Jenner Institute, University of Oxford)
|
Developmen of a new virus-like particle (VLP) vaccine for blood-stage Plasmodium |
A significant challenge for vaccine immunologists is the identification of effective formulations of an antigen that can induce the high levels of antibody required to protect against complex parasites. We have recently established a novel ‘plug-anddisplay’ approach to enable the production of viruslike particles that can array antigens that have been refractory to genetic fusion. We now wish to assess this system for proof-of-concept using an improved second-generation immunogen against the PfRH5 antigen. This antigen has been shown to induce broadly-neutralising antibodies against the blood-stage human malaria parasite Plasmodium falciparum. |
£38,192 |
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Teresa Lambe Jenner Institute, University of Oxford |
Prof Sarah Gilbert (Co-I), The Jenner Institute, University of Oxford
|
Pandemic Preparedness for Endemic Viral Disease in West Africa |
Filoviruses (Ebolaviruses & Marburg virus) and Arenaviruses (Lassa virus) are endemic in several West African countries and are causative agents for viral haemorrhagic fever. There is a clear need for vaccines that confer protective efficacy against Ebola, Marburg and Lassa viral infection. This research proposal focuses on the development of a discrete number of vaccines which can be manufactured and deployed in pandemic preparedness for the next haemorrhagic fever outbreak caused by Ebola, Marburg or Lassa fever viruses. We aim to generate proof-of-concept data supporting subsequent clinical trials. |
£48,239 |
|
Gregory Murray Liverpool School of Tropical Medicine |
JEA Parker, PJ McCall (PI) (Vector Biology Dept, LSTM) |
InFliTE: mosquito behavioural simulation package for rapid evaluation of control tools |
Disease vector control methods are under constant pressure to innovate, iterate and improve; whether to combat insecticide resistance, exploit new knowledge of vector biology or to accommodate changes in abiotic conditions. Similarly, control tools are sought that may increase efficacy, reduce costs and improve usability. However, testing the designs of new tools requires time and resources. |
£33,127 |
|
Mark Paine Liverpool School of Tropical Medicine |
Hanafy Ismail - LSTM |
New tool to predict insecticide resistance: development of Activity Based Probes to identify metabolic resistance genes in tropical disease transmitting insects |
Insecticide resistance is the major barrier to disease control. Insects contain >100 P450 genes that metabolise xenobiotic compounds. Detoxification due to elevated expression of one or more P450s is a major cause of resistance. Chlorfenapyr is a new pro-insecticide product being introduced for malaria control that is activated and inactivated by P450s. We can design ABPs that rapidly identify the individual P450s that metabolise target compounds. This will be applied to fast track the identification of CFP metabolising P450 enzymes for the development of a diagnostic ‘pre-resistance’ platform for monitoring augmenting and resistance P450 markers ahead of the resistance curve. |
£48,140 |
|
Steve Ward Liverpool School of Tropical Medicine |
Prof G. Biagini (CI - LSTM), Prof P. O’Neill (CI – University of Liverpool), Dr G. Nixon (CI – University of Liverpool), Dr Fabian Gusovsky (CI – Eisai Ltd) |
Facilitating Candidate Selection of E209 - a tetraoxane based rapidly acting antimalarial |
E209 is a tetraoxane based rapidly acting antimalarial currently in development which has been invited for candidate selection by MMV. To complete this process, a key toxicological study needs to be repeated to include a recovery period omitted in the original study. Funds are sought to carry out a 7-day dose range finding toxicity study in rats with a 14-day recovery period. Completion of this study will facilitate candidate selection by MMV. Funders GHIT have indicated that this endorsement by MMV would enable them to release funds to progress the compound through a pre-clinical package to first-in-man studies. |
£48,239
|
2016/17 |
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Alvaro Acosta-Serrano Liverpool School of Tropical Medicine |
Dr Mark Paine (VBD-LSTM); Dr Rosemary Lees; Helen Williams (LITE-LSTM); Prof Pedro Oliveira (UFRJ, Brazil) |
Controlling malaria transmission using environmentally ‘friendly’ sugar baits |
Blood feeding insects (BFI) are vectors of the most prevalent diseases, with a worldwide disease incidence of over 1 billion cases and more than 1 million deaths annually. Control of BFI typically involves the use of neurotoxic insecticides like organophosphates and pyrethroids. Furthermore, the spread of insecticide-resistance in vector populations demands development of novel approaches to block transmission of vector-borne diseases (VBD). In this project, we aim to evaluate the suitability of insect tyrosine metabolism inhibitor, Nitisinone, in Attractive Targeted Sugar Baits (ATSB). Nitisinone-based ATSB may represent a highly specific and more ‘environmentally friendly’ solution to block transmission of VBD. |
£ 28,843.52 |
|
Emily Adams Liverpool School of Tropical Medicine |
Luis Cuevas - LSTM |
Novel Probe Technology for Multiplex Molecular Diagnostics |
Molecular diagnostics are commonly used for the simultaneous identification of multiple pathogens. Standard molecular machines can identify < 5 markers per reaction. Recently we have developed tests capable of identifying 8 antimicrobial resistance (AMR) markers, but this is the absolute limit of our multiplexing ability. The patented Multiplex Probe Amplification (MPA) technology developed by GeneFirst enables us to multiplex up to 30 targets, which could allow more comprehensive viral panels or AMR profiles. In this project, we will collaborate with GeneFirst to design probes for an 11-plex viral panel and transfer this technology to the QuRapID platform (BioGene) for direct from blood fever panel diagnostics. We will also design a 20-plex AMR assay to be used on stored isolates. |
£ 40,713.08 |
|
Giancarlo Biagini Liverpool School of Tropical Medicine |
Prof Stephen Ward (LSTM); Prof Paul O’Neill (UoL); Prof Rosemary Rochford (University of Colorado); Dr Fabian Gusovsky (Eisai Ltd) |
In vivo Safety Assessment of the 8-aminoquinoline lead analog SL-6--41 |
Identification of a safe and effective primaquine replacement that offers prophylaxis, transmission-blocking activity and radical cure of relapse malaria is a high priority. We have recently developed a second-generation 8-aminoquinoline, known as SL-6-41, which has been designed to have a lowered haemolytic potential. In vitro assays indicate that SL-6-41 retains efficacy against liver stage P. falciparum, as well as early (I-III) and late (IVV) sexual gametocyte stages. In this project we wish to assess the safety of SL-6-41, in particular the potential for haemolytic toxicity, in a specialised G6PD-deficient human RBCengrafted NOD-SCID mouse model. Demonstration of safety in this model would result in the accelerated progression of this compound into a drug development programme. |
£ 45,480.11 |
|
Alister Craig Liverpool School of Tropical Medicine |
Chris Moxon (University of Liverpool); Dr. Kentaro Yoshimatsu (Eisai Co. Ltd., Tsukuba, Japan) |
Selecting modulators of PAR signalling as adjunct therapies for cerebral malaria. |
Artemisinin reduces overall mortality from severe malaria but does not improve outcome in the subgroup of children with cerebral malaria (CM) who die from rapid progression of brain swelling, typically in the first 24 hours after hospital admission. Drugs to stabilise blood brain barrier (BBB) function and prevent progression of brain swelling are needed. Recent findings indicate the PAR-signalling axis as a key mediator of BBB breakdown. We will use a coculture model of brain endothelium and infected erythrocytes to down-select existing PAR modulators for their ability to restore BBB function and to identify leads for clinical testing. |
£ 42,500.60 |
|
Nicholas Feasey Liverpool School of Tropical Medicine |
G Biagini, C Parry (LSTM), Malick Gibani, Celina Jin, Andrew Pollard (All Oxford Vaccine Group, Jenner Institute) |
Pharmacokinetics of azithromycin and ciprofloxacin in the management of typhoid fever |
Acquisition of antibiotic resistance, either by mutation or horizontal gene transfer, often incurs a fitness cost. Development of multiple resistances usually incurs a cumulative fitness cost. However, in some instances these resistance determinants interact to either increase or decrease this cumulative fitness costs in a process known as epistasis. We aim in this project to determine if there are treatment regimens that can maximise this fitness cost leading to rapid replacement of multi-drug resistance strains of Escherichia coli following cessation of treatment. |
£ 40,374.78 |
|
Sarah Gilbert The Jenner Institute, University of Oxford |
Dr. Sarah Sebastian (Jenner Institute, University Of Oxford) |
Development and testing of MVA VerOx |
The replication-deficient poxvirus vector MVA is being used to produce vaccines against many pathogens such as malaria, tuberculosis, Ebola, and other tropical diseases. However, the ability to manufacture the vaccine is hindered by the lack of suitable accessible cell lines. We will develop a modified version of MVA (MVA VerOx) that can be manufactured to high titre in the widely available Vero cell line which will remove a major barrier to the use of this safe and highly immunogenic vector in multiple vaccines. |
£ 46,598.47 |
|
Gareth Lycett Liverpool School of Tropical Medicine |
Rosemary Lee (LITE); Dave Malone (IVCC) |
In vivo screening of resistance breaking compounds |
Great strides are being made in the development of novel and repurposed compounds that break insecticide resistance. As a spin off to basic research into mechanisms of resistance in mosquitoes, we have developed a system in which these novel insecticidal compounds can be rapidly tested in genetically defined mosquitoes for their resistance-breaking efficacy. This prototype system is now being used by industry to prioritise their passage down the deployment pipeline. This CiC award is needed to expand the range of GM mosquitoes available for screening that will encompass the main mechanisms of resistance. |
£ 31,166.92 |
|
David Moore London School of Hygiene & Tropical Medicine |
Kate Gaskell (LSHTM) |
International MDRTB contact e-registry to enhance surveillance and contact management, create platform for research and generate real-time observational cohort. |
3 million household contacts are exposed to MDRTB annually but optimum management of them is unclear. Results of trials of preventive therapy are expected post-2021, potentially offering a therapeutic option. For now, WHO advises 6-monthly surveillance for 24 months but countries struggle to deliver this. In Bhutan and Somaliland, we will implement an electronic registry, populated by TB nurses during contact tracing using a simple Android-based app, through the established DHIS- 2 platform. This will systematize and improve contact follow-up, simultaneously generate a large international observational cohort, and create a ready-to-go line list of subjects eligible for further preventive therapy. |
£ 35,478.21 |
|
Mark Paine Liverpool School of Tropical Medicine |
Prof Rasmita Raval (UoL, Interdisciplinary Research Centre); Helen Williams (LITE) Rosemary Lees (LITE/LSTM); Mark Rowland (LSHTM) |
Development of smart materials for insect vector control |
Insecticide treated materials such as bed-nets and sprayed walls are principle methods of vector control. However, wide variation in insecticide efficacy is found when measuring killing efficiency (bioassays) on different surfaces. Very little is known about the molecular detail of insecticides on surfaces. The UK Interdisciplinary Research Centre (IRC) in Surface Science is at the forefront of mapping molecular behaviour at surfaces. This will be applied to determine exactly how insecticides are deposited on surfaces and how to maximise their application. This will be used for the development of smart materials capable of enhancing presentation of compounds for maximum bioefficacy. |
£ 43,802.56 |
|
Christine Rollier The Jenner Institute, University of Oxford
|
Prof Andrew POLLARD (Jenner Institute, University Of Oxford); Dr Christina Dold (Oxford Vaccine Group); Dr Malick Gibani (Oxford Vaccine Group) |
Development of a novel bivalent vaccine to prevent both Salmonella Typhi and Paratyphi infections |
The aim of this project is to accelerate the development of a novel bivalent vaccine against enteric fever, based upon a recently described virulence factor common to both Salmonella Typhi and Paratyphi. Enteric fever is a major global-health problem, affecting more than 20 million people in tropical low and middle-income countries. A bivalent vaccine would be a particularly cost-effective approach to improving health in the affected areas. We have created viral-vectored vaccines expressing key subunits of the typhoid toxin, and will compare their immunogenicity and protective capacity in order to select and progress the optimal candidate into clinical development. |
£ 49,860.49 |
|
Mark Taylor Liverpool School of Tropical Medicine |
Dr Kelly Johnston (LSTM); Prof Paul O’Neill (University of Liverpool); Dr W. David Hong (LSTM/UoL); Dr Dale Kempf, Dr Tom von Geldern (AbbVie) |
Drug target deconvolution in the obligate intracellular bacterium, Wolbachia: a chemical proteomic route to discovering novel antibacterial targets |
Lymphatic filariasis and onchocerciasis are parasitic diseases that can inflict severe disability. Targeting an essential bacterial symbiont, Wolbachia, with drugs leads to death of the adult worms: an important advance over currently used treatments. The Anti-Wolbachia (A·WOL) consortium has discovered thousands of potential new drugs that kill Wolbachia, but the specific targets within the bacteria are unknown. This project will utilise chemical biology techniques to identify the proteins targeted by selected anti-Wolbachia drugs with the aim of developing workflows and technologies to identify novel antibacterial targets and tools to monitor resistance. |
£ 46,598.47 |
|
Steve Ward Liverpool School of Tropical Medicine |
Prof G. Biagini (LSTM), Prof P. O’Neill (University of Liverpool), Dr Ann Rawkins (PHE, Porton Down), Dr D. Hong (University of Liverpool), Dr G. |
Development of pyrazolopyrimidines as anti-tuberculosis agents – hit identification, confirmation and hit-to-lead optimisation |
The co-investigators have identified novel pyrazolopyrimidines with in vitro activity against Mycobacterium tuberculosis and favourable DMPK properties. In this MRC CiC we wish to undertake proof-of-concept studies to determine the in vivo efficacy of this class of inhibitors in a validated Mtb rodent model (PHE, proton Down). In addition, a more detailed SAR of the pyrazolopyrimidines will be undertaken using both existing in-house and newly synthesised pyrazolopyrimidines tested against a number of Mtb in vitro assays including MDR Mtb clinical isolates. If successful, these data will form the basis of a full drug discovery programme. |
£ 50,984.32 |
|
Sam Willcocks London School of Hygiene & Tropical Medicine |
Prof Brendan Wren (LSHTM); Dr Mark (Gardner, Salvensis) |
Development of Methylcitrate Metabolism Inhibitors, a Novel Class of Antibiotic for Chronic Intracellular Infections |
We have invented a new class of antibiotic that selectively targets intracellular infection. Such infections are the cause of chronic diseases caused by pathogens such as Mycobacterium tuberculosis and Burkholderia pseudomallei. Modern antibiotics are poor at treating chronic disease, and they are associated with drug resistance, high cost and duration of treatment, and often relapse and spread of the pathogen. We aim to optimise the best compound design for in vivo activity in the mouse model, so that we can move towards clinical testing of a single novel antibiotic. |
£ 46,598.47 |