|
PI |
Institution |
Co-Is and institutions |
Title |
Project Summary |
Award amount |
|
Ana Cubas Atienzar |
LSTM |
Tom Fletcher (LSTM), Gary Kobinger (UTMB), Emily Adams – (GADx) |
Towards the development of a pan-lineage point-of-care test for Crimean-Congo Haemorrhagic Fever |
We aim to develop the first pan-lineage lateral flow assay (LFA) for detection of Crimean Congo Haemorrhagic Fever (CCHF) for rapid diagnosis at the point-of-care to improve patient triage, treatment, and outcomes. As CCHF is genetically diverse, we will perform fine epitope mapping on our collection of monoclonal antibodies targeting the CCHF Nucleoprotein to identify the best candidates for a pan-lineage LFA. The LFAs will be developed in collaboration with our commercial partner GADx, enterprise leading in development of rapid diagnostics and the prototypic LFA will be evaluated against a panel of CCHF isolates comprising all lineages at our collaborators in UTMB. |
£47,696.37 |
|
Anita Milicic |
Oxford |
Eleanor Stride, University of Oxford, Daniela Ferreira, Oxford Vaccine Group and LSTM |
Improving the durability of protection against malaria using a novel formulation for slow-release vaccine delivery |
The modality of vaccine delivery is key for achieving good efficacy. Recent animal studies suggest that a priming dose delivered gradually over two weeks leads to significantly more durable response to vaccination. |
£55,559.19 |
|
Caroline Wright |
Pirbright |
Linda Dixon (TPI), Carrie Batten (TPI), Hanneke Hemmink (ILRI), Anna Lacasta (ILRI) |
Establishing challenge models for African swine fever virus genotypes circulating in Africa |
A collaboration between the International Livestock Research Institute (ILRI), Kenya, and The Pirbright Institute (TPI), U.K., this project aims to establish a panel of ASFV isolates at ILRI to be used in challenge models for vaccine studies, testing levels of protection against relevant genotypes of ASFV currently circulating in Africa. The project will support The Transforming Animal Health Solutions and Services for LMIC (TAHSSL) platform based at ILRI. As part of this, ILRI’s clinical research facilities provide services to clients (internal and external) for the implementation of clinical trials, including ASFV vaccine trials, following VICH GCP standards. |
£40,162.20 |
|
David Lalloo |
LSTM |
Mainga Hamaluba & James Watson (The University of Oxford), Nicholas Casewell & Michael Abouyannis (LSTM) |
Preparedness to undertake a phase II clinical trial of two broad-spectrum, affordable, and orally administered therapeutics for treating snakebite envenoming |
Snakebite causes over 100,000 deaths and 400,000 disabilities each year, predominantly in the rural tropics. LSTM has identified two lead repurposed compounds (marimastat and unithiol) that show great promise as orally administered, affordable alternatives to antivenom. However, there are major barriers to conducting snakebite clinical trials, causing a translational bottleneck. |
£47,920.85 |
|
Eleanor Stride |
Oxford |
Anita Milicic & Sandy Douglas, Jenner Institute, University of Oxford |
Demonstration of new single-dose vaccine technology towards a first-in-human clinical application |
Incomplete vaccination remains a major issue in disease eradication. Single dose vaccines that combine initial and booster doses could provide an effective solution to improve global coverage. A multidisciplinary team at Oxford University has developed a high precision microfluidic system for creating microparticles that enable vaccine release after a tuneable lag period. Equivalent immunisation to conventional vaccination has been demonstrated successfully in a mouse model. To enable clinical translation this project seeks to scale up the system for GMP (good manufacturing practice) compliant production and develop a single dose formulation of a licenced rabies vaccine. |
£56,127.25 |
|
Ellie Barnes |
Oxford |
Gerardo Montalvo Zurbia Flores (UoO), Mala Maini and Leo Swadling (UCL) |
Development of a Universal Coronavirus Vaccine based on the highly Conserved SARS-CoV-2 Core Replication-Transcription Complex (RTC) -UNICORN |
SARS-CoV-2 remains a threat to global health: Mortality from COVID-19 remains high in vulnerable individuals and the emergence of variants has led to escape from vaccine-mediated immunity. This has highlighted the need of novel vaccines against existing coronaviruses, and those emerging in the future. Cellular immune responses targeting the highly conserved core replication-transcription complex (RTC) are associated with an “abortive” SARS-CoV-2 infection, and vaccines generating immune responses against this region may generate highly cross-reactive immunity against all coronaviruses. We propose to develop novel RTC vaccine candidates in viral vectored and mRNA platforms. |
£43,850.10 |
|
Giancarlo Biagini |
LSTM |
Paul O’Neill and W. David Hong (UoL), Giancarlo Biagini, Steve Ward (LSTM), Eric Nuermberger, John Hopkins, USA. |
Developing novel 1,2,4-thiadiazoles as antituberculosis agents |
The project team has identified a series of 1,2,4-thiadiazoles with potent in vitro activity against Mycobacterium tuberculosis, 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 class of inhibitors in a validated Mtb infection rodent model. In addition, in-depth profiling, including mode of action/resistance studies will be undertaken using complementary microbiological and 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. |
£47,500.00 |
|
Helen McShane |
Oxford |
Elena Stylianou |
Optimising multivalent vaccination approaches for tuberculosis by two strategies: (i) targeting the respiratory mucosa and (ii) with mRNA vaccines. |
An improved vaccine is urgently required to control the tuberculosis epidemic, responsible for more than 1m deaths/year. Bacillus Calmette-Guerin, the only licenced vaccine, is unable to control the epidemic, however its efficacy against childhood forms of disease, necessitates its continued administration. |
£47,390.75 |
|
Joanna Bacon |
UKHSA |
Chris Moon (UKHSA-Porton), Khondaker Miraz Rahman (KCL). Sharon Kendall (RVC), Tanya Parish (SCRI) |
Identification of the mode of action for new generation nitrofuran isoxazolines; potential new antibiotics for tuberculosis |
Through an existing and successful UKHSA-KCL partnership, we have developed a new antibiotic, containing a nitrofuran isoxazoline chemical scaffold (JA-series), to combat multidrug resistant (MDR) tuberculosis (TB). These compounds are chemically unique, and kill Mycobacterium tuberculosis (M.tb), including dormant bacteria, via a potential new mechanism of action. JA-series compounds are active against Pretomanid-resistant M.tb and could have utility as a replacement for/addition to, Pretomanid, which is a recently approved nitroaromatic antibiotic. |
£69,701.50 |
|
Kirsty McHugh |
Oxford |
Lloyd King & Simon Draper (University of Oxford), Robert Moon (LSHTM) |
Development of a novel bivalent vaccine for Plasmodium vivax Malaria |
The assessment of novel Plasmodium vivax vaccine antigens is a significant challenge due to a lack of long-term in vitro culture systems for testing vaccine efficacy against this human parasite. To overcome this, novel transgenic parasite assay platforms, using closely related parasite species modified to express P. vivax antigens, have been developed to screen vaccine-induced antibodies. This powerful new system can now be used to downselect the most-promising next-generation vaccine candidates. Here, we will design, produce, and test a novel recombinant bivalent vaccine for P. vivax, screening for functional antibody responses that are associated with protection against clinical malaria. |
£47,405.00 |
|
Nadina Wand |
UKHSA |
Roger Hewson (UK Health Security Agency & LSHTM) |
Development of a rapid point-of-care lateral flow CRISPR diagnostic assay, SHERLOCK, to detect Crimean-Congo Haemorrhagic Fever Virus. |
Crimean-Congo Haemorrhagic Fever virus (CCHFV) is a WHO priority pathogen requiring urgent development of diagnostics tools. Point-of-care diagnostics, such as Lateral Flow tests, are able to deliver rapid and accurate results in affected limited-resource areas, improving patient prospects and limiting outbreaks. CRISPR-based diagnostic assay, SHERLOCK, to detect CCHFV was previously developed with the support of the MRC CiC Fund and shown to be highly sensitive, delivering results within 10 minutes. We propose to adapt the developed fluorescence-based assay to a lateral flow format, utilising a universal test strip, eliminating complex specialised detection systems, and generating rapid, easy to interpret results. |
£44,419.15 |
|
Nicholas Casewell |
LSTM |
Janet Storm (LSTM) |
Discovery and development of human PAR1 inhibitors as new oral therapeutics for preventing haemorrhage caused by snakebite |
Snakebite causes devastating injuries and kills 140,000 people/year. Haemorrhage and coagulopathy are the most commonly observed, potentially lethal, systemic effects. Our pilot data shows that venom disrupts the endothelial cell barrier, causing leakage, but that it can be reversed by adding a drug that targets endothelial cells via antagonism of PAR1. Further, oral delivery of the PAR1 antagonist vorapaxar shows efficacy against systemic envenoming in vivo. In this study we will define the generality of snake venoms that act on barrier function and determine the inhibitory potency of vorapaxar, before identifying and defining the efficacy of novel PAR1 inhibitors. This research may lead to new, affordable oral drugs to improve treatment of snakebite. |
£48,546.90 |
|
Richard Pleass |
LSTM |
Munir Iqbal, Pirbright |
Evaluate the potential of AstraZeneca’s sialic acid tag technology for treating influenza viruses with Fc molecules |
Many important viruses, including influenza A virus (IAV) and Newcastle Disease virus (NDV), use multivalent binding to sialic acid to infect cells and cause disease. We are engineering fragmentcrystallisable (Fc) molecules derived from antibodies that are rich in sialic acid. These sialylated Fc’s interfere with the ability of IAV & NDV to bind cell surface sialic acids thereby preventing virus entry into the cell. The sialylated Fc has compelling advantages over competing solutions (see Table 1 below for influenza). Here we wish to determine if AstraZeneca’s sialylation technology offers improved virus binding and neutralisation by the Fc. Please see letters of support attached. |
£46,836.90 |
|
Roger Hewson |
LSHTM |
Zhugen Yang (Cranfield University), Laura Bonney (UKHSA), Nazif Elaldi (Cumhuriyet University Hospital, Sivas) |
Origami paper device for point of care diagnosis of Crimean-Congo haemorrhagic fever |
The World Health Organisation has identified Crimean – Congo haemorrhagic fever (CCHF) as a public health emergency requiring urgent research, particularly for diagnostic tests that can be used at the point of care. We will develop a low-cost, easy-to-use ‘Origami’ device for CCHF virus that will work in low resource settings, deliver results in ~45 minutes at the point of care. It brings together expertise in CCHFV virology, diagnostics and genomics developed by Hewson (LSHTM & UKHSA), and novel paper microfluidics and diagnostics developed by Yang (Cranfield). It will be worked up with UKHSA and evaluated on CCHF patients in Turkey. |
£50,559.00 |
|
Russell Stothard |
LSTM |
Co-investigators: Jayne Jones, Lucas Cunningham, Alex Juhasz, LSTM, Will Nevin, LSTM/DMS with Jaco Verweij, Elisabeth Tweesteden Hospital, Tilburg, |
When ‘splitting worms’ is not just ‘splitting hairs’: New TaqMan® primer-probe diagnostics to detect and differentiate Strongyloides stercoralis and Strongyloides fuelleborni in clinical and environmental samples. |
Our focus is upon strongyloidiasis, with twofold intentions. First, we address a newly appreciated in-house diagnostic gap of the Clinical Diagnostic Parasitology Laboratory (CDPL), LSTM. Second, we promote better public health surveillance of zoonotic strongyloidiasis. Our coordinated workplan, of 4 work packages, spans 9 months, where we |
£37,250.00 |
|
Stuart Ainsworth |
LSTM |
Rob Smith, University of Liverpool (UoL) |
A feasibility study of manufacturing antivenom from the milk of venom hyper-immunised dairy cows: A low cost, high yield and economically viable solution to the global antivenom availability crisis? |
Antivenoms, critical for treating envenoming globally, are produced via hyperimmunization of horses and subsequent purification of antibodies from their plasma, a hugely costly, low-yield process. Here we will investigate if immunisation of dairy cows can lead to the recovery of therapeutically viable antibodies from milk by-products at scale, in what we predict will be a high-yield, low cost and economically viable alternative to current antivenom manufacturing. Simultaneously, we will perform a thorough market assessment to assess potential commerciality and regulatory issues of such manufacturing to enable rapid access to follow translational funding. |
£59,098.55 |
|
Susana Campino |
LSHTM |
Kevin Maringer (Pirbright Institute), Mary Cameron, Taane Clark and Mojca Kristan (LSHTM) |
Application of field-deployable surveillance tool to enhance molecular xenomonitoring of multiple vector borne diseases |
Molecular xenomonitoring (MX) is a disease surveillance method that involves the detection of pathogens in vector populations, which can be used as a proxy for human/animal infections. MX has been successfully applied to monitor lymphatic filariasis in elimination stages. However, MX is dependent on the use of polymerase-chainreaction methods, which need expensive instruments and are not field-deployable. We have developed multiplex Lateral-Flow Recombinase-Polymerase-Amplification assays to detect DNA from malaria and leishmania parasites in vectors. We propose to extend our assays to capture additional pathogens, including RNA viruses, and enable the delivery of a field-ready approach for multivector-borne disease surveillance. |
£46,756.62 |
|
Taane Clark |
LSHTM |
Susana Campino (LSHTM), Colin J. Sutherland (UKHSA-MRL and LSHTM), Deborah Nolder (UKHSA-MRL and LSHTM) |
Rapid portable malaria drug-resistance genotyping using isothermal nucleic acid diagnostic methods |
Progress on malaria control has stalled in the past few years and is threatened by the emergence of diagnostic evasive and antimalarial resistant Plasmodium falciparum populations. Parasite resistance to artemisinin has emerged and spread in Southeast Asia, and recently in Africa, notably Rwanda and Uganda. Here we propose the continued development of a Recombinase Polymerase Amplification-based Lateral-Flow Rapid Diagnostic and genotyping Test (“RPA-LF-RDT”) to simultaneously detect the presence of P. falciparum and antimalarial resistance markers, including but not limited to Kelch13 gene mutations associated with artemisinin resistance. This project directly addresses the urgent surveillance-based objectives outlined in the 2022 WHO Malaria Report. |
£47,442.55 |
|
Teresa Lambe |
Oxford |
none |
Design and development of cross-protective New World arenavirus vaccines |
New World (NW) arenaviruses are endemic in regions throughout the Americas, dictated by the presence of their predominantly rodent hosts. Able to cause haemorrhagic disease in humans with high case fatality, millions are at risk with limited tools to reduce outbreaks. We plan to design a cross-protective vaccine by cloning the glycoprotein precursor (GPC) gene, an established target of protective immunity, from the two most widespread NW arenaviruses into the ChAdOx1 vector. Additionally, in partnership with Moderna, we intend to design and evaluate a poly-cistronic mRNA vaccine construct, encoding the GPC from five of the known NW arenaviruses capable of causing human disease in South America. |
£40,682.80 |
|
Young Chan Kim |
Oxford |
Sir Andrew Pollard & Amy Flaxman (University of Oxford). Fiona van der Klis & Gerco den Hartog (Dutch National Institute for Public Health, and the Environment (RIVM), Netherlands) |
Development of a sensitive and specific serological assay based on Luminex technology for detection of antibodies to Salmonella Typhi and Paratyphi |
Enteric fever is a serious public health concern. It is caused by Salmonella enterica serovars, Typhi and Paratyphi which are responsible for 11-18 million and 3.4-5.4 million infections per year, respectively. A reliable rapid diagnostic test is needed to reduce overdiagnosis and over-use of antibiotics and improve the disease burden estimates in endemic area. Diagnosis is often complicated by the lack of a reliable gold standard test. We have previously developed ELISAs based on recombinant Salmonella antigens. In this project, we aim to develop a multiplex assay capable of detecting antibodies against multiple Salmonella antigens to allow sensitive and specific diagnostics for timely clinical management, improved surveillance, and immunogenicity assessment of novel vaccines. |
£47,479.10 |