NIHRDataInsights/HRCSData huggingface dataset:
Title: The Development of Novel Antimicrobial Materials to Prevent Pathogenic Infections
Funder: Innovate UK

Abstract: Antimicrobial resistance, AMR, is globally responsible for 1.2 million annual fatalities. Antimicrobial resistance, AMR, is already responsible for 1.2 million annual fatalities. Failure to address the issue by 2050 could result in 10 million deaths per year, costing the global economy £66 trillion. To put this into context, the predicted death rates for cancer will be 8.2 million by the same year. As current treatment and preventative antimicrobial technologies fail, minor injuries and simple surgeries, such as a scratch on the knee, could soon become fatal. To address this global healthcare emergency the World Health Organisation, WHO, have highlighted there is a clinical unmet need for novel technologies that can treat and prevent such pathogenic diseases. At MetalloBio we are directly answering this unmet need, in line with the UK Government's 20-year vision to control and contain AMR by 2040\. As part of highly skilled team, MetalloBio have developed two lead antimicrobial additives, that can be incorporated into different materials and coatings. These materials can be applied to medical and non-medical applications such as catheter coatings, orthopedics, wound care, paints, textiles and food packaging. MetalloBio's antimicrobial functionalised materials will be able to prevent infection, transmission and spread of harmful pathogens, improving human health and patient quality of life. The antimicrobial additives have higher activities than clinical antibiotics and current antimicrobial additives, but crucially this activity is retained against drug-resistant bacteria, including those highlighted by the WHO as a critical priority. The complexes have a modular synthesis, like Lego, we can exchange the "building blocks" of our additives to make a whole series of these complexes. Additionally, they are non-toxic and highly active when incorporated into different polymeric materials. As these complexes are highly innovative, and radically different from anything on the market, the likelihood of emergence of resistance is highly reduced. This project will directly build upon preclinical data on the additives, and proof-of-concept coating studies, to optimise our antimicrobial materials. Antimicrobial and antibiofilm efficacy studies will be completed on a broad-spectrum of pathogens and the coatings will be applied to a number of different materials to broaden the application potential. The recent COVID-19 pandemic highlighted the catastrophic effects of a global pandemic, increasing MetalloBio's technology's application potential will help in the fight to prevent AMR causing the next pandemic. MetalloBio will work closely with commercial partners to ensure the technology will be applicable in commercial environments.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: INFECTION
Title: Heavy Metal-Free Quantum Dot Testing Kit for the Accurate and Rapid Visual Detection of SARS-CoV-2 from Saliva Samples
Funder: Innovate UK

Abstract: Simple, fast and reliable methods for the detection of SARS-CoV-2, the pathogen that causes Covid-19 in humans are still badly needed to reduce the spread of the pandemic and mitigate its impact on health care systems and on the overall socioeconomic status. Current methods are either complicated and expensive as in the case of PCR; or non reliable and inaccurate as in the case of typical immunoassays. Also, most of the current methods require the use of nasopharyngeal swabs, which can be unpleasant, require training and sending to a specialist laboratory for analysis, often taking several days before results. In this project a point-of-care testing kit will be developed to enable the rapid and easy detection of SARS-CoV-2 or future flu epidemics from saliva samples using a multiplexed immunoassay enabled by fluorescent quantum dot nanoparticles (QDs). Unlike conventional immunoassays that suffer from high inaccuracy, or the PCR methods that suffer from complexity, high cost and result delays, the brightness and multiplexing ability of QDs will provide a reliable detection capabilities that can be performed quickly without prior training and at a lower cost. In this project, a new type of non-toxic QDs (VIVODOTS(tm) nanoparticles) that was developed by Nanoco Technologies, Ltd for biomedical applications will be linked to targeting antibodies against two or more structural proteins in the virus. Once the functionalized QDs with various colour codes come in contact with the SARS-CoV-2 viral particles in the saliva sample, they will bind to the virus and generate unique spectral emission under blue light source. The unique spectral emission will occur only in the presence of the actual virus. The QDs in this type of application offer a number of advantages over conventional fluorescent dyes and colloidal gold, including bright and coded emissions from a single excitation source and low reflectance interference, which is ideal for platforms based on surface detection like lateral flow sticks or paper strips. The proposed concept of this diagnostic kit is versatile and agile as it can be modified quickly to respond to potential future mutations or to new outbreaks caused by other types of contagious pathogens.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: Development of Key Technologies for Real-Time Diagnosis, Surveillance and Interventionof Resistant-Bacterial Infections Based on Nanopore Sequencing
Funder: Innovate UK

Abstract: The proposed project aims to tackle two of the major hurdles in the fight against AMR, new drugs and new diagnostics. The new diagnostics will utilise cutting edge UK technology (Oxford Nanopore sequencing) to provide test results with unprecedented depth of information within 6 hours as opposed to the current technologies which routinely take 24-48 hours. The approach to new drugs entails developing "Potentiators" - agents that can permeabilise the cell wall of bacteria allowing the use of established antibacterial compounds. The Potentiators in this project target Gram-negative (OPT-200) and Gram-positive (OPT-1) bacteria and both have novel modes of actions representing first-in-class antibacterial programmes. The focus of this project will be on Hospital Acquired Pneumonia (HAP) and subset of HAP Ventilator Acquired Pneumonia (VAP). HAP/VAP are important infections throughout the world and are a major cause of morbidity, mortality and increases in hospital stay resulting in escalation of healthcare costs. The long-term goals of this project are to provide rapid diagnosis technology for HAP/VAP that can be combined with a potentiator treatment regime. Finance Summary Table – How to complete this section


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: Development of a Therapeutic mRNA Vaccine for COVID-19 using pHion's Delivery Technology
Funder: Innovate UK

Abstract: As infections with SARS-CoV-2 continue to rise with associated healthcare and economic implications, there is a race on to develop a vaccine to prevent the disease. RNA vaccines are designed to encode the genetic sequences of antigens of a disease, in this instance SARS-CoV-2 and evoke an appropriate immune response. There are several pipeline mRNA vaccines for SARS-CoV-2 that are designed to evoke a prophylactic response but as yet there is no therapeutic vaccine in development. To make a vaccine therapeutic, a particular type of immunity is required known as a CD8+ response. Phion Therapeutics (Belfast SME) have a technology that when added to mRNA, creates a vaccine that produces a CD8+ response. We get this response because we can deliver the vaccine into the correct cells (antigen presenting cells) using a cell penetrating peptide (RALA) as a delivery vehicle which is not recognised as foreign and bypasses the innate response. RALA is designed to cross cellular membranes and fuse with endosomal membranes when the pH lowers which facilitates the release of the mRNA antigens into the cytosol without any associated toxicity. We are the only company to have this peptide to deliver the vaccine. The vaccine itself is a genetic cargo (mRNA) designed to code for the antigens in a particular disease, in this instance multiple immunogenic proteins from SARS-CoV-2\. RALA is adept at condensing all three mRNA into nanoparticles which are lyophilised and uniquely stable at room temperature without losing functionality. Studies are designed to create a RALA/mRNA vaccine, validate baseline characteristics in humanised mice expressing the ACE-2 receptor, followed by determining the response in hamsters and then ferrets through outsourced challenge studies with SARS-CoV-2\. Finally, we will develop a regulatory framework to ensure progression to the clinic. Outputs from this project are designed to provide definitive evidence of a robust prophylactic and therapeutic response using in vivo models. With a comprehensive data package, by the end of this 18 month project we will have the candidate vaccine to progress to toxicology studies. We believe that the RALA/mRNA technology marks the advent of a new generation of therapeutic vaccines that could clear viral infections on a global scale. Most importantly, this platform technology for therapeutic vaccination will be made readily available to other industries and academics across the UK. With validation of automated scalability by the Centre for Process Innovation, pHion is confident of the supply chain.


Research activity codes: 3.4 VACCINES;5.1 PHARMACEUTICALS
Health categories: INFECTION
Title: Antiviral Reusable Plastic Cup Suitable for Events and Festivals (SafeEnviroCup)
Funder: Innovate UK

Abstract: The coronavirus pandemic has reversed the move towards reusable plasticware and other materials, with single use product utilisation increasing as a way of reducing the risk of infection spread. As businesses and events open back up this return to disposable plastic use will put a massive strain on both resources and the environment. Recup (Project Lead) provide branded (event details), washable, reusable, recyclable cups to events and venues including Lord's Cricket Ground, Royal Ascot and Arsenal football club. Consumers pay a small deposit per cup, encouraging return, and at the end of the event Recup collects, cleans and reuses (or recycle into new cups if branded with a specific event) the cups at more events. Concerns over using reusable cups (due to Covid) is that they pose an infection risk to customers and those collecting them, and residual virus may remain following cleaning (particularly if cleaned at the venue/festival if reused at the same event). CodiKoat (Project Partner) is developing a surface treatment using a novel (IP protected) combination of antimicrobial metallic nanoparticles and surface electrochemistry that provides a weak electric current. This disrupts the virus membrane and is effective within seconds and has long lasting anti-microbial properties (up to two years). CodiKoat has already tested the viability and stability of the materials coating on substrates. By applying this to self-adhesive tapes and films they are creating a product that can be used on any solid surface, instantly rendering it antimicrobial. This removes the need for constant surface disinfection, significantly reducing cleaning costs and the hazardous waste generated. The aim of this project is apply the CodiKoat antiviral surface treatment to in mould labelling (IML) to create a safe, reusable and branded cup suitable for use at events. This will enable Recup to supply event venues with a unique product and significantly grow market share.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: INFECTION
Title: Replacing animal models in fungal pathogen research: An in vitro Titan virulence assay for the human fungal pathogen Cryptococcus neoformans
Funder: National Centre for the Replacement, Refinement and Reduction of Animals in Research

Abstract: This Studentship aims to reduce and replace the use of animal models (mouse, rabbit) in


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: INFECTION
Title: Characterising Mycobacterium tuberculosis in the human lung; developing new tools for antimicrobial drug discovery through the SH-TBL clinical trial
Funder: National Centre for the Replacement, Refinement and Reduction of Animals in Research

Abstract: Tuberculosis (TB) remains a considerable socio-economic and health problem. TB is among the top ten causes of death worldwide and the leading cause of death by an infectious agent. 1.8 million people died from TB in 2015 and more than 2 billion people are latently infected. The problem is exacerbated by the emergence of multiple-drug resistant (MDR-TB) and extensively-drug resistant (XDR-TB) disease. The World Health Organisation End-TB strategy depends on the introduction of new tools, such as novel drug therapies, vaccines and diagnostics by 2025 to succeed. This cannot be achieved with current methodologies and development pipelines. Currently, no in vitro model is able to reproduce the localised microenvironments and granulomas of the tuberculous lung and the most widely-used animal model, the mouse, does not share this pathology. Thus, in vitro and many animal models for TB do not mimic conditions of the human lung and therefore have limited power to predict the efficacy of new drugs in patients. This has created a bottleneck where novel vaccine and drug candidates are not followed up due to the limited usefulness and scalability of animal models. New models rooted in the host-pathogen dynamic of the human tuberculous lung will be more representative of human disease and therefore more useful to the development of novel interventions. Such innovative clinically-relevant models will replace some animal models in early drug discovery programmes. This timely and original project will use molecular profiling tools to characterise Mycobacterium tuberculosis (M.tb) in lung tissue from TB patients undergoing lung resection surgery. Lung resection remains a treatment option for TB, this discard tissue is being collected in an ongoing clinical trial (SH-TBL) to understand the immunology of TB lung lesions. This project, working alongside the clinical trial, will identity novel TB vaccine candidates expressed at the site of pathology, where vaccines and drugs are targeted, and develop a model using insights from both M.tb phenotype and lung lesion immunology to replace animals in early TB drug discovery research. This project will also demonstrate that human tissue can provide an ethical, viable and superior alternative to animal models for human infectious disease research and has the potential to replace experiments currently conducted in a range of laboratory animals.


Research activity codes: 5.1 PHARMACEUTICALS;5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: INFECTION
Title: Insects as models to study the impact of antibiotics and microbiota therapies on the human gut microbiome: reducing the use of animals in research
Funder: National Centre for the Replacement, Refinement and Reduction of Animals in Research

Abstract: The human gut contains microbial communities (gut microbiota) that have profound effects on health and well-being, including immune development, metabolism and infection resistance. Disturbances in these beneficial microbial communities are linked to numerous diseases; it is critical to understand the composition and dynamics of the microbiota so that we may positively modulate this ecosystem to promote health. Of particular importance is the gut microbiota of new-born babies. Disturbances in this developing and unstable community appears to have significant short- and longer-term impacts on overall composition, and is linked to increased risk of chronic inflammatory diseases, allergies and infection. Importantly, early life microbiota can be influenced by numerous factors, with antibiotic treatment suggested as among the most significant, leading to an immediate reduction in microbial abundance and species diversity. Antibiotics are highly prescribed during the first few years of life and the impact that the various antibiotic regimens have on the early life microbiota over time is unclear. Furthermore, exposing the early life gut microbiota to significant levels of antibiotics may create an important reservoir of resistant strains and of transferable resistance genes, the so called resistome, which may correlate with the increasing incidence of antibiotic-resistant and more infective pathogens, which is directly relevant to the current global antimicrobial resistance (AMR) threat. After these antibiotic-induced disturbances several approaches could potentially be used to restore the microbial ecosystem into one able to promote health, including targeted dietary modulations and/or bacterial therapies such as probiotics. However, to understand the impact of these factors and to probe specific mechanisms underpinning microbiota changes is extremely challenging in humans, particularly infants, especially performing long-term longitudinal studies. Rodent models, e.g. mice, are routinely used mammalian models that in principle can be used for microbiota studies, however there are significant ethical and cost issues.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: INFECTION
Title: Experimental evolution of Pseudomonas aeruginosa in media replicating the conditions of the upper and lower airways
Funder: National Centre for the Replacement, Refinement and Reduction of Animals in Research

Abstract: Pseudomonas aeruginosa (Pa) is an important bacterial pathogen in people with cystic fibrosis and other chronic lung conditions. During early infection, Pa adapts to the environment of the respiratory tract, leading to long-lasting, difficult to treat infections. The ways in which Pa adapt to the lung environment, and the host factors driving this adaptation are poorly understood. Better understanding of Pa in-host adaptation would help identity new diagnosis and treatment approaches and help in the fight against accelerating antimicrobial resistance (AMR).


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFECTION
Title: Towards Multiplexed In Vivo Phenotypic Screening to Improve Antimicrobial Drug Discovery
Funder: National Centre for the Replacement, Refinement and Reduction of Animals in Research

Abstract: Antimicrobial-resistant infections are prevalent worldwide, with drug-resistant strains emerging for all currently available antimicrobial drugs and the burden of disease estimated to be ~50,000 deaths/year in Europe and North America. Resistant microbes include bacteria such as Pseudomonas aeruginosa, and eukaryotes such Toxoplasma gondii, the causative agent of toxoplasmosis and a protozoan parasite for which resistance to front-line drugs is a growing concern. New therapeutic targets and drugs to treat these infections are urgently needed. Unfortunately, drug-discovery research and development (R&D) is costly in terms of time, money, and animal lives, with estimates of the cost of bringing a drug to market being $1-2.5 billion USD. Improvements in drug-discovery efficiency and success would reduce both cost and the number of animals used. Drug-discovery pipelines suffer from high failure rates, in part due to an inability to search for new drugs in vivo. The lack of knowledge of pathogen gene products essential for growth in vivo represents a significant gap in our knowledge. This limits our understanding and ability to develop drugs that can efficiently target pathogens in the context of an infection. These genes are an underutilized resource in the search for novel therapeutic targets. The ability to study host-pathogen interactions in vivo represents an exciting and scientifically important opportunity for the discovery of new biology, novel drugs and drug targets. It is a final frontier of host-interaction biology that remains inaccessible to many of the powerful high-throughput approaches shown to be successful in the past due to the experimentally intractable nature of the in vivo environment.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: INFECTION
Title: BBSRC-DEFRA Global Coronavirus Research Network Call
Funder: Department for Environment, Food and Rural Affairs

Abstract: The Global Coronavirus Research Network Call is an interdisciplinary research coordination programme, which will enable international networking and collaborative working for the coronavirus research community. The funded network will draw together the major global research and industry actors working on veterinary and human coronaviruses to compare, contrast and advance the understanding of coronaviruses. The main aims of the Network will be to embrace a One Health approach, facilitating research collaborations and serving as a communication gateway for the global coronaviruses research community; integrating with the human coronavirus research community; bringing together experts to analyse gaps and identify research priorities, and conduct strategic research to better understand coronaviruses


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);3.5 RESOURCES AND INFRASTRUCTURE (PREVENTION);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: INFECTION
Title: SE0569: Coronavirus Prevalence in GB Bats (Active and Passive Surveillance)
Funder: Department for Environment, Food and Rural Affairs

Abstract: Earlier research into the origin of the 2003 SARS-CoV-1 outbreak resulted in the discovery of many SARS-like bat coronaviruses, most originating in the Rhinolophus genus of horseshoe bats. A number of coronaviruses (CoV) that are closely related to SARS-CoV-2 have been detected in bats but their origins, evolution and mode of transmission into humans remains unclear. Currently bats are considered the most likely natural reservoir of SARS-CoV-2, however, with more than 1200 species of bats globally and the >3000 CoVs estimated to be circulating in bats (Anthony et al., 2017), identifying the potential intermediary host, relative susceptibility and potential evolutionary/recombination events arising from SARS-like bat CoVs poses challenges. In this project we hope to further our understanding of the distribution and diversity of bat CoVs in GB bats, making full use of our unique access to bat material submitted as part of the Defra funded Rabies Passive Surveillance Programme. Oropharyngeal and anal swabs will be collected from selected bats and screened using a pan Coronavirus RT-PCR.In addition, we aim to study CoV distribution in a population of serotine bats within a number of roosts in Southern England and Wales. It is hoped that swab samples (oropharyngeal, fur and rectal swabs) and blood will be collected from approximately 20 individual serotine bats from a number of roosts between Mid-May and August 2022. The swab samples will be screened using a pan CoV RT-PCR. If resources allow any residual serum (after screening for EBLV-1 antibodies) will be tested using available CoV serological assays. Please note this NED proposal supports the related EBLV-1 Active Surveillance proposal, ensuring sufficient funds are available to complete the field and laboratory tasks required for both CoV and EBLV-1 prevalence studies. Active bat surveillance field sampling skills at APHA have lapsed. The Active Surveillance NED projects will allow those skills to be resurrected ensuring APHA’s capacity to investigate disease incursions and emergence is current and optimal. The associated Home Office Licence will be renewed to include the additional sampling (fur, anal) and aims (CoVs surveillance).Material generated through this NED project will be used to assess host genetic susceptibility in an additional NED proposal.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: INFECTION