|
PI |
Institution |
Co-Is and institutions |
Title |
Project Summary |
Award amount |
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Cassandra Modahl |
LSTM |
Dr Stephanie French and Dr Michael Abouyannis Liverpool School of Tropical Medicine, Liverpool, Prof Francis Ndungu KEMRI-Wellcome Trust Research Programme (KWTRP), Kenya. Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Prof Mainga Hamaluba KEMRI-Wellcome Trust Research Programme (KWTRP), Kenya. Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Dr Abdirahman Abdi KEMRI-Wellcome Trust Research Programme (KWTRP), Kenya. Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Dr Jamie Soul Computational Biology Facility, University of Liverpool |
Using clinical samples to identify adjunct immunomodulatory therapies for the prevention of local tissue injury in snakebite victims |
Snakebite envenoming causes over 400,000 life-altering disabilities annually. Antivenom, the only treatment, has adverse side-effects and is ineffective for local tissue injury, which often results in permanent sequelae. Host immune responses may play a role in envenoming associated local tissue damage. We aim to characterise host responses to snakebite with transcriptomics and immunological methods, leveraging clinical samples from a recent study on Kenyan snakebite patients. This project represents a world-first in generating gene expression profiles from snakebite victims, enabling an understanding of the host response to snakebite and, by stratifying based on tissue injury, identify therapeutics for snakebite tissue damage. |
£59,949.54 |
|
|
Young Kim |
Oxford |
Prof Sir Andrew Pollard Ashall Professor of Infection & Immunity, and Honorary Consultant Paediatrician. Director of the Oxford Vaccine Group. Prof Daniela Santoro Rosa The Federal University of Sao Paulo (UNIFESP), Brazil. Prof Jose Ronnie Vasconcelos The Federal University of Sao Paulo (UNIFESP), Brazil. |
Development of a mRNA vaccine against Chagas disease |
Chagas disease is a significant public health concern, particularly in the Americas. It is caused by Trypanosoma cruzi (T. cruzi), which affect over 8 million people worldwide, with more than 10,000 annual deaths and 70 million at high risk of infection. Existing licensed medications face multiple challenges, including a high incidence of adverse reactions and reduced efficacy during the chronic stage of infection and there are currently no approved vaccines. Previously, we developed viral-vectored Chagas vaccines expressing key antigens which provided 100% protection in mice against T. cruzi infection. In this project, we will test mRNAs expressing these promising antigens. Additionally, a combined viral-vectored and mRNA approach will be evaluated for its potential to enhance protection. |
£44,651.01 |
|
|
Miles Carroll |
Oxford |
Dr Emily Adams, Liverpool School of Tropical Medicine, Professor Peter Horby, University of Oxford, Professor Ray Owens University of Oxford/RFI |
Development of a point-of-care lateral flow test for Nipah virus infection |
Nipah virus infection can present with non-specific symptoms and has a high case fatality rate (~40-75%). A rapid point-of-care lateral flow assay (LFA) is urgently needed to enable rapid triage and prevent outbreaks. The University of Oxford in collaboration with The Liverpool School of Tropical Medicine (LSTM) and Global Access Diagnostics (GADx) aim to develop a prototype rapid LFA for Nipah virus infection. This project seeks to utilise existing nanobody reagents (University of Oxford) and generate new reagents (GADx and LSTM) to develop a prototype LFA that can then be taken from proof-of-concept through the design and development pathway at GADx. |
£49,302.00 |
|
|
Ash Otter |
UKHSA |
Alex Richter (AR) University of Birmingham, Scott Jones (SJ) UK Health Security Agency, Sian Faustini (SF) University of Birmingham, Jennifer Heaney (JH) University of Birmingham, Jake Dunning (JD) University of Oxford |
Development of a lateral flow device for detecting anti-MPXV specific antibodies as a mechanism to conduct serosurveillance and target at-risk individuals for vaccination |
With the recent localised spread of Monkeypox virus (MPXV) within the UK, and ongoing outbreaks in endemic countries, there is a necessity for better surveillance and targeted vaccination in at-risk individuals, however, this is currently limited by the accessibility of diagnostics. This project aims to develop both a cost-effective and sensitive lateral flow device (LFD) for detecting anti-MPXV antibodies. This proposal is for the development and optimization of a point-of-care anti-MPXV IgG and IgM antibody LFD, with extensive technical and clinical validation, leveraging the expertise of both UKHSA in Mpox immunology and the University of Birmingham in LFD design. |
£54,308.89 |
|
|
David Weetman |
LSTM |
Dr Walter Fabricio S. Martins LSTM, Dr Lara Ferrero Gómez University of Jean Piaget, Cape Verde |
A Field Pilot Study for MELT (Mosquito Eco-friendly Light Trap): a cost-effective and compact entomological surveillance tool for vector-borne disease control programmes. |
Mosquito surveillance provides crucial data on the presence and abundance of disease vector species to target and evaluate control measures in resource-limited settings and to identify emergent threats. Nevertheless, mosquito surveillance often remains sporadically implemented in vector-borne disease endemic regions, owing to the time and cost of maintaining mosquito traps. In response, we are developing the Mosquito Eco-friendly Light Trap (MELT), a compact, economical solar-LED and odour-lure mosquito trap. After promising proof-of-principle testing, MELT has been engineered for scaled-up production, and here, we aim to perform a pilot field study to evaluate MELT’s capacity to catch mosquitoes in field conditions. |
£49,746.03 |
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|
Kevin Maringer |
Pirbright |
Prof. Susana Campino London School of Hygiene and Tropical Medicine Dr. Isabelle Dietrich The Pirbright Institute Dr. Mojca Kristan London School of Hygiene and Tropical Medicine Dr. Matthew Higgins London School of Hygiene and Tropical Medicine |
Application of molecular xenomonitoring in a lateral flow test format for multiplexed monitoring of vectorborne viruses and their animal reservoirs and insect vectors in low-income settings |
Vector-borne viruses cause a major and rising global public health impact, primarily in tropical and subtropical low- and middle-income countries. Monitoring circulating viruses with their vectors and animal reservoirs is essential for effectively implementing disease control measures, but resource intensive. We will here bring to a field-ready state our multiplexed molecular xenomonitoring assays in a simple-to-use lateral flow test format that detect vector-borne viruses in blood-fed mosquitoes and faeces, while also identifying the species of vector and host sampled. We will determine optimal sampling windows and will assess the field readiness of our tests in Tanzania and Puerto Rico. |
£49,015.15 |
|
|
Nick Casewell |
LSTM |
Dr. Michael Abouyannis & Prof. Ymkje Stienstra LSTM, UK, Prof. Wuelton Monteiro & Dr. Marco Sartim Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Brazil, Prof. Geoff Isbister University of Newcastle, Australia |
Assessing the utility and predictive value of point of care coagulation tests as early identifiers of snakebite envenoming in resource poor settings |
Snakebite causes >100,000 deaths annually, and haemotoxicity characterised by coagulopathy is the most common manifestation of systemic envenoming. In low resource settings, a 20-minute whole blood clotting test is used to detect coagulopathy and to dictate eligibility for antivenom therapy. However, sensitivity of this test is imperfect, leading to treatment delays, misallocation of antivenom, and poor patient outcomes. Here we will address these limitations by assessing the utility of point-of-care coagulation devices for more accurate and earlier detection of snakebite envenoming in three diverse LMIC settings. We anticipate our findings will demonstrate point-of-care coagulation testing is a valuable new tool for the clinical management of snakebite. |
£49,052.00 |
|
|
Kirsty McHugh |
Oxford |
Charlotte Deane Department of Statistics, University of Oxford, Alissa Hummer Department of Statistics, University of Oxford, Ubaid Qadri High Performance Software Engineering (HPSE) Group, Science and Technology Facilities Council (STFC) UKRI |
Development of an in silico affinity maturation platform for therapeutic monoclonal antibodies |
Monoclonal antibodies (mAbs) are an appealing prophylactic strategy for the control of infectious diseases but are often limited by the in vivo levels required to achieve protection. This proposal aims to develop an in silico platform to improve mAb potency by enhancing the binding affinity. Experimental methods for measuring the effect of mutations on mAb affinity are time-consuming and expensive. Computational methods offer promise but typically suffer from a trade-off between speed and accuracy. This study plans to validate and, in collaboration with STFC, optimise the software speed of Rosetta Flex ddG for in silico affinity maturation using antimalarial mAbs. |
£42,888.89 |
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|
Lloyd King |
Oxford |
Dr Barnabas Williams Biochemistry Department, University of Oxford |
Development of a trivalent vaccine for Plasmodium falciparum malaria. |
The development of a blood-stage Plasmodium falciparum vaccine has been hampered by a lack of conserved antigens. We previously developed a new fusion vaccine, “R78C”, which combines the conserved P. falciparum antigens CyRPA, and the EGF (7-8) fragment of RIPR. Recent data from our humanised-mouse monoclonal antibody project show that potent synergising epitopes within RIPR were removed from the R78C construct. In addition, portions of CyRPA elicit non-neutralizing antibodies. This project will use build on this antibody analysis to redesign and downselect a second-generation R78C constructs for future clinical testing. |
£49,102.80 |
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|
Anusyah Rathakrishnan |
Pirbright |
Linda Dixon (LD) , Ana Reis (ALR), Raquel Portugal (RP) and Priscilla Tng (PT) The Pirbright Institute |
Predicting cross-protection of African swine fever virus (ASFV) vaccines against diverse genotypes circulating in Africa |
ASFV causes an economically important pig disease. Vaccine development is focused on the pandemic ASFV genotype II. In Africa, twenty-four ASFV genotypes are present but information on the cross-genotype protective ability of vaccines is limited. We showed that our modified live genotype II vaccines induce protection against genotype I but not IX. Ex vivo assays that predict protection have been developed. We will use these to analyse samples from our previous vaccination experiments. This will predict ability of our genotype II MLV to cross-protect against ASFV genotypes from Africa. The results will inform vaccine development for ASFV in Africa. |
£40,238.40 |
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|
Giancarlo Biagini |
LSTM |
Paul O’Neill University of Liverpool, David Hong University of Liverpool, Eric Nuermberger John Hopkins, USA., Steve Ward LSTM, Daire Cantillon LSTM |
Developing a novel oxazolidinone hybrid (AWZ4L02) front-runner as new antituberculosis agent |
The project team has identified a frontrunner, AWZ4L02, from a series of oxazolidinone hybrids, with potent in vitro activity against Mycobacterium tuberculosis (Mtb), acceptable metabolic stability and good oral exposure in mice. In this project we propose to carry out proof-of-concept studies to determine the in vivo efficacy of this new class of inhibitors in a validated Mtb infection rodent model. In addition, in-depth phenotypic profiling, including against Telacebec- (Q203, an experimental drug in phase 2 clinical trial) and linezolid-resistant Mtb, resistance studies, e.g. propensity of resistance, that will be undertaken using complementary genomics approaches to investigate the potential of this series for further development. If successful, these data will form the basis of a full-scale anti-tuberculosis drug discovery programme. |
£49,800.00 |
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|
Steve Ward |
LSTM |
Joanna Bacon and Chris Moon UK Health Security Agency, David Hong and Paul O’Neill University of Liverpool, Giancarlo Biagini and Daire Cantillon LSTM |
The activity of BTZ-endoperoxide hybrids against M. tuberculosis in relevant phenotypic states; towards the development of a new antitubercular therapeutic |
Targeting mycobacteria in drug tolerant persisting states is an important strategy in the development of effective drugs to combat tuberculosis (TB). While actively replicating bacteria are responsible for the symptoms and transmission of TB, a substantial portion of them can transition into other phenotypic states that are hard to reach with current drug regimens and can result in persistent infection, making it a significant challenge in TB treatment. Hypoxic environments of the granuloma, where the organism resides during chronic TB disease, can lead to adaptive phenotypic changes that are brought about by a regulon of genes that is controlled by the two-component sensor regulator DosRST. The investigators have developed novel BTZ-endoperoxide hybrids with favourable in vitro efficacy and in vivo PK profiles. Endoperoxides have previously been shown to inhibit DosRST signalling by inhibition of DosR, DosS or DosT leading to the attractive possibility that these novel drug hybrids could be effective against persister Mtb. Validation of this approach would be pioneering and here, we seek support to use an established chemostat-based approach to provide proof-of-concept data that if successful, will form the basis of a full-scale anti-tuberculosis drug discovery programme. |
£67,137.37 |
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|
Thomas Edwards |
LSTM |
Dr Stefanie Menzies , Dr Ana Cubas Atienzar and Dr Emily Adams LSTM |
Accelerated development of a rapid graphene biosensor for dengue fever |
Dengue Fever causes 400 million infections per year and is attributed to 40,000 deaths. Rapid diagnostic tests for Dengue are poorly sensitive, meaning there is still a reliance on laboratory-based RT-qPCR, which delays diagnosis. |
£49,695.42 |
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|
Rosemary Lees |
LSTM |
Katherine Gleave LSTM |
Optimising and validating the host-free tunnel test: a more affordable, practical, and ethical tool for evaluation of insecticide treated nets (ITNs) |
The tunnel test is a standard method for laboratory evaluation of insecticide treated bednets but relies on the use of a live rabbit or guinea pig to stimulate blood feeding by test mosquitoes. An animal handling licence and ethical approval are therefore required. A version of the tunnel test has been developed which replaces the animal with artificial attractants, and preliminary results are promising. Funding is sought to complete optimisation of the method, and to generate validation data to support the uptake of the new method by testing facilities and a recommendation of the method from the WHO. |
£48,664.04 |
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|
Isabelle Dietrich |
Pirbright |
Prof. Alain Kohl (AK) LSTM |
Validation of novel recombinant interferons for treatment of tropical arboviral fevers. |
There is an immediate need for innovative approaches to prevent and manage arboviral diseases. These account for one-fifth of the global infectious disease burden, primarily affecting tropical and subtropical regions. |
£53,362.69 |
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|
Simon Draper |
Oxford |
Dr Francesca Donnellan, Dept of Biochemistry & Kavli Institute, University of Oxford Dr Kirsty McHugh Dept of Biochemistry & Kavli Institute, University of Oxford, Prof Richard J. Pleass Liverpool School of Tropical Medicine, Liverpool University |
Assessing the impact of epitope on the efficacy of engineered monoclonal antibody-based drugs against human malaria. |
The recent success of the first monoclonal antibody (mAb) trialled as seasonal prophylaxis for malaria confirmed mAbs can be a useful tool in achieving global malaria eradication targets. However, this mAb targets only the pre-erythrocytic stage of the malaria parasite. To reach eradication targets, potency and efficacy must be improved in the next generation of malaria mAb treatments against multiple stages of the parasite’s complex lifecycle. This project aims to enhance the potency of mAbs targeting the leading blood-stage parasite antigen, PfRH5, using a proprietary Fc-engineering platform. |
£26,059.34 |
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|
Anna Roca |
LSHTM |
Abdul K Sesay, Thushan De Silva, Bakary Sanyang MRCG@LSHTM and Uni Sheffield |
Impact of intra-partum azithromycin on neonatal mycobiome – a pilot study before the implementation and scaling up of intrapartum azithromycin (MYCO) |
Clinical trials in low-middle-income countries found intrapartum azithromycin reduces maternal sepsis and neonatal infections, but not mortality or neonatal sepsis. The recommendation of scaling up this intervention needs additional data on unintended consequences to the newborn, as azithromycin reaches the baby through breastmilk. Our hypothesis posits that azithromycin alters neonatal sepsis pathogens, increasing fungal infections while decreasing bacterial infections resulting in a net zero impact. Testing this hypothesis is crucial for informed intervention scaling-up as for example fungal infections are only a concern during the rainy season. This pilot study bridges knowledge gaps, accelerating transitioning from discovery science to implementation. |
£36,151.81 |
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|
Steve Findlay-Wilson |
UKHSA |
Dr Dalan Bailey (DB) The Pirbright Institute Nazia Thakur (NT) The Pirbright Institute, University of Oxford Professor Teresa Lambe (TL) University of Oxford Professor Simon Graham (SG) The Pirbright Institute Dr Stuart Dowall (SD) UKHSA |
Defining the success criteria for pan-henipavirus vaccines |
Whilst Nipah and Hendra are the only established pathogenic henipaviruses, the strong likelihood remains that a known unknown, i.e., a previously uncharacterised henipavirus, will emerge to initiate an epidemic – as was the case for SARS-CoV-2 in 2019 (at the time, an uncharacterised coronavirus of bats). There is an urgent need to establish the parameters for pan-henipavirus vaccines, e.g., whether vaccination |
£84,660.00 |
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|
Philip McCall |
LSTM |
Alphaxard Manjurano National Institute for Medical Research, Tanzania, Luca Facchinelli LSTM |
Is the resting behaviour of African malaria vectors vulnerable to minimal targeted IRS? |
The resting behaviour of many endophilic vectors is targeted for control using indoor spraying of residual insecticides (IRS). Potentially very effective, IRS is costly, slow to deliver, and logistically challenging for low-to-middle income countries. Recently, we demonstrated that the resting location of endophilic Aedes aegypti is modulated by indoor temperature and relative humidity (RH) clines. Mapping this dynamic resting behaviour enabled us to target mosquitoes efficiently, drastically reducing the insecticide-treated area required for control to <10%. Here, we will test our hypothesis that endophilic sub-Saharan anophelines are affected similarly and that mapping their resting behaviour will enable similar levels of reduction in IRS application without loss in performance. |
£45,750.15 |
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|
Joseph Mugisha |
LSHTM |
Rogers John Mukasa Lead applicant (MRC/UVRI & LSHTM), Nathan Mubiru Co-applicant (MRC/UVRI & LSHTM), Ronald Makanga Co-applicant (MRC/UVRI & LSHTM), Hubert Nkabura Co-applicant (MRC/UVRI & LSHTM) |
Feasibility of using point of care machines in diagnosing anaemia among pregnant women and children in South-western Uganda – Kalungu district; A Population based study |
Anaemia is a global concern with the most vulnerable being children and pregnant women within the malaria endemic areas. Point of care (POCT) instruments have had increased utility in the diagnosis of anaemia. |
£43,242.34 |
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