NIHRDataInsights/HRCSData huggingface dataset:
Title: Hosts, Pathogens and Global Health
Funder: Wellcome Trust

Abstract: To solve the problems of neglected and emerging diseases an integrated approach to infectious disease biology is needed. We must understand the biology of the pathogen and its interaction with the host, immune mechanisms that contribute to disease outcome, and the ecological and epidemiological factors that determine disease spread. If the future leaders in global health are to exploit knowledge of the full range of pathogen and host interactions, from core molecular processes to understanding host-pathogen interactions in the field, including co-infections, zoonoses and evolutionary dynamics, coupled with an appreciation of the wider societal context, we must prepare them from the outset of their PhD. Since establishment in 2016 the Wellcome Trust “Hosts, Pathogens and Global Health” programme has developed a unique interdisciplinary and international research training structure providing expertise spanning infectious disease biology from molecular to evolutionary and epidemiological scales. Our key goals are: • To train a cadre of infection biologists skilled in interdisciplinary approaches to disease control and well versed in the opportunities of quantitative, theoretical and experimental approaches. • Use the community and mentorship ethos within Edinburgh and between our international partners to build a life-long supportive network of next-generation researchers working across disciplines to combat infectious disease.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: INFECTION
Title: Dual-Acting Aspartyl Protease Antimalarials
Funder: Wellcome Trust

Abstract: "Malaria is one of the world's most devastating diseases of humans and results in over 400,000 deaths annually. novel therapies are urgently required to populate the antimalarial clinical portfolio, as the current therapeutics that treat this disease are becoming less effective due to emerging resistance. A collaboration between Dr David Olsen from Merck & Co., Kenilworth, NJ USA (known as MSD outside the US and Canada) and Professor Alan Cowman from the Walter and Eliza Hall Institute (WEHI}, has demonstrated that malaria aspartyl protease enzymes are attractive drug targets, as they perform essential functions for survival in liver, blood, and sexual stages of the parasite life cycle. Through screening aspartyl protease inhibitor libraries, the collaboration has identified novel drugwfike hit compounds that are potently active against the malaria parasite. The proposed lead optimization research aims to increase potency against the parasite whilst maintaining selectivity, progressing to a Iab development stage clinical candidate."

Lay abstract: Malaria is a major global health problem with increasing drug resistance to first line therapies. For the past 1.5 years, Wellcome Trust, via a Seeding Drug Discovery Award ‘early’ project, funded Merck and WEHI in an antimalarial effort. The team focused on a series of molecules that have been transformed into impressive (low nM – pM) intracellular potency versus Plasmodium falciparum that are over 10-fold more potent than benchmark antimalarial drug chloroquine. Investigative biology/biochemistry has revealed that the most potent leads exhibit dual targeting of two conserved and essential protease drug targets (plasmepsin IX and plasmepsin X). Both of these enzymes are responsible for critical processing of multiple other proteins required for the parasite to productively invade and egress from various cell types along the pathway of its lifecycle. The dual targeting of such essential enzymes, both with significant down-stream consequences, likely explains the robust pharmacodynamic effect observed in the mouse models of efficacy and the very high barrier to resistance of the leads. Key program deliverables: With the next round of funding, the team will: 1) Within lead optimization, advance this program to identify a robust clinical development candidate 2) Understand the best combination agent for clinical dosing with a PM IX/X candidate 3) Advance the candidate into preclinical safety derisking studies 4) Establish human clinical safety 5) Achieve proof of concept in a malaria human infection study The team’s goal is to identify a novel malaria treatment that results in a cure in with <4 doses of drug

Research activity codes: 5.1 PHARMACEUTICALS
Health categories: INFECTION
Title: A pipeline of drugs for leishmaniasis and Chagas disease
Funder: Wellcome Trust

Abstract: Visceral leishmaniasis and Chagas disease are neglected tropical diseases that cause substantial suffering and an estimated 60,000 deaths each year. Current medicines are inadequate – issues include limited efficacy and unacceptable toxicity. There is a need for new, effective and safe drugs to save lives and improve quality of life for people in low-income countries with these diseases. Our fully-integrated team, led by Professor Paul Wyatt, Dr Jose Fiandor and colleagues at the University of Dundee and at GSK has the substantial leadership, experience and infrastructure required to develop drug candidates suitable for clinical trials. We are already making substantial progress: we have identified two candidate drugs for visceral leishmaniasis and improved the methodology and systems to develop drugs for this and Chagas disease. But a greater pipeline of candidate drugs is required to ensure clinical success. Our goal over the next five years is to deliver at least two, potentially three, new drug candidates suitable for clinical trials for either of these diseases.

Lay abstract: Neglected parasitic diseases, visceral and cutaneous leishmaniasis, and Chagas’ disease cause substantial suffering and an estimated 60,000 deaths annually world-wide. This death toll and inadequate available drugs, for reasons including lack of efficacy and unacceptable toxicity, amounts to a major unmet medical need. Consequently, development of effective and safe drugs will save many lives and improve the quality of life and economies within the developing world. Our established, fully integrated GSK/Dundee team brings together the broad range of expertise required to discover these much-needed drugs. The team combines world renowned parasitology, extensive experience developing molecules that can kill the parasites, and the substantial expertise and infrastructure required to develop drug candidates suitable for clinical trials. The team is making substantial progress, having already identified one candidate drug for visceral leishmaniasis, with another potential candidate drug close behind and having improved the methodology to develop drugs for these diseases. However, a pipeline of candidate drugs is required to fully address the unmet medical need. These achievements ensure that we are uniquely positioned to deliver our aim of a stretched goal of three, with a minimum of two, drug candidates suitable for clinical trials for any of these diseases within 5 years.

Research activity codes: 5.1 PHARMACEUTICALS
Health categories: INFECTION
Title: Thailand Africa and Asia Programme - GBP Core
Funder: Wellcome Trust

Abstract: The Wellcome Thailand AAP has conducted high quality impactful research for 40 years on infectious diseases of major public health concern, leading to the widespread adoption of new approaches and treatments for many of them including malaria, melioidosis, and rickettsial infections. In our fifth decade we will focus on ensuring sustainable impact and influence on policymakers by strengthening our research network and developing the capabilities of our partner institutions. Our vision is to: 1. Through research continue to address public health problems with regional and global relevance, using cutting edge approaches to seek affordable and deployable solutions to disease prevention, diagnosis and patient management. 2. Maximise our public health research’s uptake and impact, incorporating health economics analysis and goal-driven engagement with policymakers, national academic institutions, hospitals, industry partners, communities and the general public. 3. Work with our local host institutions to increase their national and global impact by integrating activities including training programmes, joint research projects, and supporting partner-led programmes to translate research into policy and practice. Our goal is to improve life quality and expectancy by reducing the adverse impact of infectious diseases, which account for much of the disparity in health metrics between low and high income countries.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: INFECTION
Title: Malawi Liverpool Wellcome Trust Programme - Core Award
Funder: Wellcome Trust

Abstract: We will achieve internationally excellent translational science to benefit human health with a focus on sub-Saharan Africa. MLW is built around excellent laboratories, strategically located in the largest hospital in Malawi, closely linked with the community and an integral part of the medical school. These relationships provide a valuable opportunity replicated in few centres in Africa to study major health issues spanning both community and hospital. We will manage two major Programmes: (1) Preventing death from severe infection, and (2) Transmission reduction in infectious diseases and continue to publish over 100 papers/year. Over the next 5 years, we will target clinical syndromes of sepsis, meningitis, diarrhoea and pneumonia with vaccine, behavioural and clinical management strategies. We will focus on transmission of HIV, TB and malaria with improved access to care, diagnosis and treatment. In addition, a Strategic Initiative will target selected high burden chronic diseases (lung impairment, stroke, blindness), particularly related to HIV. In partnership with the College of Medicine we will deliver Training that will attract, train and retain local and international senior scientists. Through our partnership with the Ministry of Health, our Policy Aims will ensure that our research is both relevant and applied to improve human health.

Lay abstract: Low income countries like Malawi (ranked 147/181 countries in wealth) suffer very high levels of infectious disease and low life expectancy which are problems now largely eliminated from wealthy countries. Malawi is an ideal place to research these problems as the government are supportive, and we have excellent access to hospital and community patients, a large staff and superb research resources. Over the next 5 years, we will carry out research aiming to reduce the number of deaths from infection and the number of new infections occurring in the community. We have targeted the major causes of death and disease among adults and children in Malawi, including diarrhoea, pneumonia, meningitis, HIV, TB, malaria and typhoid. We plan to use vaccine research, community advice to improve health seeking behaviour, better tests for diagnosis and improved treatments to improve health in Malawi and the region. We will work with the College of Medicine to ensure that we offer an excellent research training environment for African scientists (currently 55 in training). We will work with the Ministry of Health in a new policy unit to ensure that research findings are relevant and useful to influence human health now and in the future.

Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: INFECTION
Title: Safe and Effective Antiviral Technology for diagnostics and prevention of SARS-CoV-2
Funder: Innovate UK

Abstract: The Covid-19 pandemic has caused extensive health, economic and social damage in the UK and worldwide. As countries reactivate economies, it is essential to reduce transmission risks of bioaerosols in enclosed places (e.g. public transport, workplaces, health, education, and leisure settings) and contaminated soft surfaces (textiles/face masks) using safe disinfection technologies. In response to the Covid-19 crisis, Aqdot (Cambridge-based SME), in collaboration with University of Cambridge has recently demonstrated that its platform technology, AqBit (cucurbit\[n\]urils, CBs), is a unique virucide that inhibits SARS-CoV-2-pseudovirus without harming human cells. The technology, available at multi-tonne scale, is safe for humans and the environment as evidenced in the REACH (100 tonne/annum) registration dossier. The project will be completed in the UK between Aqdot, Dr Sam Jones (cucurbit\[n\]uril understanding and virology expertise) at the Henry Royce Institute, University of Manchester, and Professors Andrew Bayly and Nik Kapur (spray generation, characterisation and development) at the School of Chemical and Process Engineering, University of Leeds. The project will focus on the development of safe and efficacious antiviral spray formulations based on Aqdot's technology to inactivate SARS-CoV-2 in soft surfaces (fabrics) and bioaerosols. The project will deliver comprehensive technical, safety data packages, including AqBit-based formulations, delivery devices specification and virucidal performance validation against SARS-CoV-2\. Scalable product demonstrators will be generated for each application (fabric and airborne virus) using hand-held spray devices for small spaces, and a regulatory strategy will be put in place to ensure quick biocidal registration. Also, the concept of automatic spray devices will be validated for use in larger enclosed spaces. The demonstrator formulation/device combinations will be designed for rapid commercialisation, upon success, as low-cost products providing readily available, affordable solutions to reduce the transmission rates of Covid-19, benefitting individuals and businesses. These products will build societal confidence to "return to normal" in the UK and beyond.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: Improved oligonucleotide synthesis for faster, more accurate COVID-19 testing
Funder: Innovate UK

Abstract: Testing people to find out whether they are infected with coronavirus is important in order to get them treated properly if they do test positive, and to keep the virus under control in the population. Programmes such as the UK Government's Test and Trace scheme work out whether the virus has infected someone by assessing whether its genetic material is present in a sample of human tissue such as a nasopharyngeal swab. There are two ways of doing this -- a test known as LAMP, which is a newer approach, or the current gold standard test, qPCR. Both tests use strands of DNA known as oligonucleotides. The use of the LAMP test has grown dramatically during the coronavirus pandemic because it uses cheap and simple equipment. However, the fact that it uses more oligonucleotides than qPCR, and the massive demand for LAMP testing, means that manufacturers are struggling to produce large volumes of high purity oligonucleotides rapidly. The oligonucleotides need to be highly pure, with no unwanted material such as DNA strands which are too short, so that the tests give accurate results. Large volumes are needed so that people can be tested repeatedly and regularly. ATDBio is a UK based company which is an expert in making the DNA needed for LAMP testing. Based on its experience it has devised a method which should enable the production of large, highly pure quantities of DNA more quickly and economically. Its new method combines reducing the amount of unwanted shorter strands produced when making oligonucleotides, with a better way of removing them and other unwanted pieces. The company already has early data suggesting that this new approach will work. In this Innovate UK project, the funds will be used to develop and research the new techniques further and assess whether the oligonucleotides they produce work in COVID-19 tests. The new oligonucleotides will then be produced on a large scale and tested independently in COVID-19 tests outside ATDBio's laboratories. ATDBio's new method is expected to increase the amount of DNA that can be produced three fold, reduce the time taken to purify it by three quarters, and increase its purity to 96%. This should make the LAMP COVID-19 tests faster and more accurate, and reduce their cost. In addition, the new techniques will be suitable for making DNA when testing for other infections, and in diseases such as cancer.


Research activity codes: 2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY)
Health categories: INFECTION
Title: Development of a SARS-CoV-2 spike protein binding assay using human epithelial cells for COVID-19 therapy discovery and development
Funder: Innovate UK

Abstract: The urgency of the current COVID-19 pandemic needs new treatments to be developed as quickly and as safely as possible. Whatever comes out of the many labs involved in these efforts needs to be tested in a variety of ways to help us know if they will work when given to people who might be infected by SARS-CoV-2, the virus which causes COVID-19\. For the virus to cause this disease, it needs to get inside some of our cells where it can survive, multiply and then infect other cells in the body. To do this, the virus first needs to latch onto our cells. For this, it uses a specific part on the outside of the virus, the 'spike', to fasten onto special parts on the outside of our cells ('receptors') to which if fits, like a key fits a lock. This project will recapitulate this first essential step of viral infection allowing us to test new treatments 'in a dish' in order to support the therapeutic discovery effort against COVID-19\. Whilst models to support this development are available using systems with purified components of cells (using the 'receptors' the virus uses for entry), or, using the intact virus, there is a lack of cellular models that can be used in a simple manner for testing the impact of drugs, and antibodies arising from vaccination, on specific steps of viral entry into human cells. We intend to develop a 'cell-based' model using human cells (including cells lining the lung, which are known to be a key site of entry for the virus) and SARS-CoV-2 purified spike protein. This biological model will enable us and our industrial partners to test their therapeutics on a very specific step vital for viral infection. We will use advanced imaging techniques to visualise this binding of the viral spike protein to human cells, and, we will then be able to test how drugs, or other agents such as antibodies generated by a vaccine, impact this specific step of viral entry. This will then enable candidate drugs to be selected as therapeutics, improved versions of drugs to be developed or support the selection of vaccines that generate protective antibodies against the virus.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: An innovative colour-change handwipe that detects surface contaminants, ensuring high hygiene.
Funder: Innovate UK

Abstract: Fresh Check Ltd. (FreshCheck) is a UK food hygiene SME with a core project team of Alex Bond (Project Lead), John Simpson (Technical Lead) and Melis Ekinci (Head of Science). FreshCheck is solving a significant unmet need by developing an affordable and simple-to-use colour-change handwipe that will detect surface contaminants and help verify/ensure hygiene. The solution will especially benefit SME food businesses that find it difficult to meet the hygiene standards/attain high food safety ratings required to access large food contracts (e.g. manufacturing for a supermarket chain) and address the public's awareness of hygiene and cleaning standards. The solution will be environmentally friendly and help reduce plastic usage resulting from current tools.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: INFECTION
Title: Treatment of critical COVID-19 patients through removal of IL-6 by magnetic blood filtration
Funder: Innovate UK

Abstract: MediSieve is a multi-award-winning medical device company developing Magnetic Blood Filtration (MBF), an extracorporeal technology similar to dialysis, in which Targeted Magnetic Particles (TB-MPs) are infused into the extracorporeal loop, binding specifically to disease-relevant targets in the patient's blood. The blood then flows through a Magnetic Filter (MF) which captures the particles and bound targets, while the remainder of the blood returns to the patient unaffected. There are 6 TB-MPs currently under development, targeting IL-6, endotoxins, IL-1ß, IL-18, CD19 and CD20\. In this project, MediSieve proposes to accelerate the development of its anti-IL-6 TB-MPs and to apply MBF as a treatment to severe COVID-19 patients in the UK and worldwide. The project will support validation in animal trials and clinical trials, regulatory approvals, and lay the foundations for widespread distribution post-project. COVID-19 studies have identified IL-6 driven hyperimmune reactions as a significant contributor to mortality with elevated IL-6 (p<0.0001) a predictor of fatality (Conti, J. Bio. Reg. Hom. Ag. 2020; Mehta, Lancet 2020). Additionally, a retrospective study of 191 hospitalised patients with COVID-19 found that over 50% developed sepsis (Zhou, Lancet 2020). By focusing specifically on IL-6 MediSieve can rapidly bring a product to market to alleviate the cytokine storm and hyperimmune reaction as well as the secondary sepsis that is the cause of significant mortality in COVID-19 patients. In vitro data suggest that adult IL-6 levels could be reduced by 90% in 4 hours. The MF has completed GLP pre-clinical animal studies and manufacturing validation; it is ready for first-in-man trials. The IL-6 TB-MPs have been validated with in vitro blood testing and are ready for animal trials. This project will accelerate development of the IL-6 TB-MPs and whole system through pre-clinical validation, manufacturing validation and regulatory approval to enable human clinical trials in preparation for full scale release.


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: INFECTION