NIHRDataInsights/HRCSData huggingface dataset:
Title: Room temperature stable solid vaccine formulations suitable for needle free delivery
Funder: Innovate UK

Abstract: Needle free delivery of a room temperature stable vaccine which has the potential to reduce dosing frequency and / or to save antigen content has been a 'holy grail' of vaccine technology. Glide Pharma has developed a needle free device (recently completed a Phase 1 clinical study) that can deliver solid formulations and can uniquely meet all three requirements. Glide has previously demonstrated user acceptability and the dose sparing effect of the technology. The aim of this project is to evaluate room temperature stability which, theroretically, should be much easier to achieve with a solid vaccine compared to a liquid formulation. Glide can revolutionise vaccine delivery with its needle free, stable and low cost vaccine technology. This will enable developed countries to be better prepared for pandemic situations and to reduce healthcare costs, and the developing countries to enjoy the full benefits of modern vaccines.


Research activity codes: 3.4 VACCINES
Health categories: INFECTION
Title: Development of a novel VLP based vaccine for malaria
Funder: Innovate UK

Abstract: Malaria remains a major cause of death, particularly in many developing countries. Currently no vaccine is commercially available and existing pharmaceuticals are becoming less and less effective due to parasitic resistance, while insecticide resistance in diminishing the utility of that intervention. Therefore, we propose to develop an new and potent vaccine using a delivery system developed by iQur Ltd and malaria antigens under development by the Jenner Institute at Oxford University. In this feasibility study, we will prepare a virus like particle (VLP), which will carry the malaria target antigens, and test these vaccines for safety, immunogenicity and efficacy in mice. VLPs are well accepted as a safe delivery system and give rise to strong immune responses. If this study is successful, we will then initiate a clinical development programme which will bring this vaccine to market


Research activity codes: 3.4 VACCINES
Health categories: INFECTION
Title: A Novel agent for the treatment of CDifficile infection
Funder: Innovate UK

Abstract: Clostridium difficile (C.Diff) Associated Diarrhoea (CDAD) is a severe form of diarrhoea which can prove fatal. Prevalence has been increasing since the late 1990s, and it is increasingly occurring outside of hospital and in previously low-risk groups. Valevia is developing a drug which has demonstrated efficacy against hyper-virulent strains of C.Diff and strains with reduced susceptibility to current therapies, is rapidly bactericidal and shows no cross resistance to currently used antibiotic classes. This project will further characterise its pharmacological profile, validate its potential to address currently unmet medical needs in CDAD and design a clinical development plan enabling the earliest possible Registration.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: INFECTION
Title: Assessing the feasibility of developing Ai2's novel anti-infective peptide technology for topical anti-fungal applications.
Funder: Innovate UK

Abstract: Ai2 is a UK-based biotechnology company specialising in novel anti-infective peptide technology combining potent antibacterial efficacy with excellent safety. Ai2 is now researching the antifungal efficacy of the technology to determine the feasibility of development as an antifungal agent. Topical fungal infections are a common and increasing health concern that cause discomfort and distress to patients and can lead to potentially fatal systemic infections. The currently available treatments have significant drawbacks including lengthy treatment time and resistance generation, therefore a more effective agent is needed. This project aims to establish the efficacy of selected peptides against relevant organisms and their safety and compatibility with human tissue. This would result in Ai2 generating a data portfolio that demonstrates the feasibility of developing our technology as an antifungal agent further.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: INFECTION
Title: Development of a new class of bacterial resistance inhibitors for the treatment of multi-drug resistant infection
Funder: Innovate UK

Abstract: The spread of multi-drug resistance (MDR) threatens to change the face of health care worldwide, crippling hospital units that rely on the ability to control infections in patients with weakened immune systems We risk returning to a "pre-antibiotic" era unless we can develop new approaches to tackling bacterial resistance. Blueberry Therapeutics aims to assess the feasibility of an innovative therapeutic approach to inhibit key mechanisms of MDR using peptide aptamers formulated with a new nanoparticle delivery system. By directly targeting the mechanisms of resistance we hope to reverse bacterial resistance and render drug resistant bacteria sensitive to treatment with already available and common antibiotics again. We aim to demonstrate the feasibility of this approach to restore antibiotic sensitivity in clinically relevant MDR bacterial species and if successful will be the first step in developing a new class of therapies with which to treat MDR infections.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: INFECTION
Title: Novel universal influenza vaccines to induce broad mucosal immunity against influenza viruses in children
Funder: SPARKS

Abstract: Flu is a serious illness caused by flu viruses in human upper airway. Both seasonal and pandemic flu cause significant number of death. The most effective way to prevent flu is vaccination. The currently used flu vaccines are based on the surface molecule HA which changes structure frequently, so a new seasonal vaccine has to be produced every year. We will test several uniquely designed new vaccines which target the part of HA that does not change thus potentially induce broad immunity against most types of flu viruses. We will test the capacity of these vaccines, if used as a nasal spray in children, to eliminate major influenza diseases.


Research activity codes: 3.4 VACCINES
Health categories: INFECTION
Title: Dendrimer based drug for life threatening infectious diarrhoeal diseases
Funder: Innovate UK

Abstract: A new dimmer switch like drug for the immune system. Infections continue to take a huge toll on human lives despite the use of powerful antibiotics. Indigix believes that this can in part be due to an overreaction of the patient's immune system to bacteria. When the body is attacked, cells of the immune system release cytokines - powerful chemicals with a mission to seek and destroy bacteria. If the storm is excessive, multiple organ failure develops and death follows. A new drug from Indigix addresses this neglected aspect of treating an infection by creating a molecular mimic of the molecule on the outside of bacterial cells (called LPS) that triggers the response. The Indigix drug, called DG, uses a dendrimer based molecule to bind to the same receptor as LPS. This reduces the cytokine response just like a dimmer switch reduces the brightness of a bulb. Using DG enables Indigix to reduce cytokines to levels that are helpful rather than harmful.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: INFECTION
Title: Phase I study to assess tolerability, safety and PK of MGB-BP-3 in healthy volunteers
Funder: Innovate UK

Abstract: MGB Biopharma is developing a new class of antibiotic originally discovered in the UK by researchers at the University of Strathclyde. The drug, MGB-BP-3, has a novel mechanism of action which means that resistant bacteria will not be a feature as is the case with existing antibiotics. The first indication to be developed is the treatment of Clostridium difficile infections and the Techology Strategy Board has provided grant funding to complete the human safety study. This drug, and potentially others from the same platform, shows promise for further development for the treatment of other infections, including MRSA and other serious life threatening infections against which existing drugs are becoming less effective due to the increase in resistant bacteria.


Research activity codes: 5.1 PHARMACEUTICALS;6.1 PHARMACEUTICALS
Health categories: INFECTION
Title: Tablet Vaccines
Funder: Innovate UK

Abstract: Acellular vaccines have an excellent record of safety and efficacy in target paediatric patients but the restricted scope of the immune response and the reduced duration of immunity compared to previous live or attenuated vaccines has led to declining protection for older patients and incomplete herd immunity. For pertussis this has resulted in a recent upsurge of cases across well vaccinated countries. The objective of this project will be to develop innovative tablet vaccine formulations to allow booster acellular vaccines to be taken orally. The formulations will aim to boost systemic antibody titres and induce a mucosal immune response resulting in improved efficacy. Self-administered oral booster vaccines will also lower healthcare costs and encourage better patient compliance, resulting in more extensive community protection within developed and developing world countries


Research activity codes: 3.4 VACCINES
Health categories: INFECTION
Title: Feasibility of site- directed delivery of endolysins for targeted antibacterial therapy
Funder: Innovate UK

Abstract: This project will test the feasibility of using bacterial quorum sensing to trigger targeted delivery of bacteriophage endolysins by a bacterial vector (B. subtilis) in an innovative approach to antibacterial therapy. In light of rapidly emerging bacterial resistance to antibiotics, novel antimicrobials that are more refractory to resistance development are urgently needed. We will evaluate the feasibility of our approach in the context of Clostridium difficile (C.diff). C.diff infections (CDI) are the most frequent hospital-acquired infections in many industrialised countries driven by the emergence of highly virulent, antibiotic -resistant, strains. Our delivery system will use gut commensal bacteria engineered to transit the bactericidal stomach as spores, germinate in the intestine, replicate and produce C.diff- specific endolysins in the C.diff –occupied micro-environment in order to maximise their potent and highly specific lytic properties. The concepts underpinning the approach are of wider application.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: INFECTION
Title: Phase I oral safety assessment of a novel antifungal for systemic fungal infections
Funder: Innovate UK

Abstract: Systemic fungal disease is a life threatening groups of infections caused by yeasts and moulds that affects people who have impaired immune systems The numbers of patients are increasing and the current threatment options are limited to three types of antifungal drug. Often these drugs have severe side effects or can't be used with other medicines. F2G has identified a new type of antifungal that works through a different mechanism. It is highly potent against many of the moulds that cause these serious infections. This project aims to develop this new antifungal drug by testing its safety in man and how it interacts with other drugs. Following this project the drug can be tested in patients suffering from serious infection.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INFECTION
Title: Virus transmission dynamics and the immune response of birds to avian influenza.
Funder: Biotechnology and Biological Sciences Research Council

Abstract: At present H5N1 avian influenza is an animal disease problem under urgent need of control. The widespread occurrence and wide host range of the H5N1 virus poses a serious threat to the human population, potentially leading to the evolution of a human influenza pandemic. Our knowledge of the behaviour of avian influenza viruses in domestic fowl and wild birds is limited. Virus infection dynamics of H7N1 low and high pathogenicity avian influenza viruses and highly pathogenic H5N1 viruses in chickens, turkeys and ducks will be compared. Extensive in-depth sequence analysis of the virus haemagglutinin gene will be undertaken to examine within-host selection of virus variants in each species- avian host range determinants. We also will determine whether in-bred chickens lines show genetic differences in susceptibility to infection and in virus shedding, and whether there are genetic differences in the immune response of the in-bred lines to infection and vaccination- these studies can provide a starting point to uncovering the genetic basis of host resistance to influenza virus infection. The immune response to infection will be studied at tissue level, and protective cellular, humoral and cytokine responses will be defined.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFECTION
Title: Cell morphogenesis in Bacillus subtilis: from genetics to exploitation
Funder: Biotechnology and Biological Sciences Research Council

Abstract: All major branches of the bacterial sub-kingdom possess a cell wall containing peptidoglycan (PG), which is a huge mesh-like network that covers the whole surface of the cell. PG consists of long glycan strands cross linked by peptide bridges. The precursors for PG are made inside the cell and then polymerized on the outside by the action of penicillin-binding proteins (PBPs). Autolytic enzymes cleave bonds in the PG in a controlled manner to allow orderly growth of the cell. The walls of Gram positive bacteria contain an almost equal mass of one or more anionic polymers called teichoic acids, the functions of which remain poorly understood. The cell wall is a crucial structure for bacteria because it opposes the cytoplasmic turgor pressure on the cytoplasmic membrane, preventing the cell from bursting, as well as providing protection from mechanical damage. The wall is also the target for the best of our antibiotics, particularly ?-lactams and glycopeptides. Despite many decades of research, many features of cell wall biogenesis remain poorly understood. The aim of this project is to identify most, if not all of the genes and proteins required for cell wall biogenesis in the experimentally tractable model Gram positive bacterium Bacillus subtilis. Then to systematically characterize the components of the synthetic machinery in terms of mutant phenotype, gene-gene and protein-protein interactions and protein localization. Selected elements of the systems will be characterized in terms of biochemical function and protein structure. New knowledge emerging from the programme will be used to design screens for small molecule inhibitors that could provide inhibitors for use as experimental reagents or antibiotic leads.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: INFECTION
Title: Community based interventions against Tsetse and Trypanosomiasis on the Jos Plateau Nigeria
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Livestock underpin poor rural livelihoods in sub-Saharan Africa, but animal health is constrained by both epidemic and endemic diseases. The former are managed by national and regional control programmes whereas individual farmers control endemic diseases, with communities and local organisations providing support in decentralised and privatised systems Animal trypanosomiasis constitutes a major endemic problem in tsetse-infested regions, reducing livestock product yields and devaluing farmers' investments - costing livestock producers and consumers an estimated US$1340 million annually. The Jos Plateau in North-Central Nigeria is a major cattle keeping area, holding ~ a million cows ( 7% of the national herd) kept by settled pastoralists practicing seasonal migration. It became tsetse infected in the early 1980's and trypanosomiasis is a recent problem in the area. While trypanosomiasis can be seen as a dual constraint to rural development its control presents a double benefit: improvements in livestock health having positive outcomes for human health well-being and development. We aim to develop novel integrated control strategies based on an understanding of the epidemiology of trypanosomiasis in domestic livestock, Epidemiological theory will be integrated with quantitative field studies where pastoralists contend with trypanosomiasis and co-exist with subsistence farmers in an area with high land pressure. Research will target (i) pastoralists for whom simple and practical decision support tools are needed for livestock management and (ii), district and national level policy makers requiring decision support for endemic disease control.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: INFECTION
Title: Molecular dissection of a novel protein-protein interaction: structure and mechanism of the staphylococcal fusidic acid-resistance protein FusB
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Fusidic acid (FA) is an important antibiotic for the treatment of bacterial infections caused by the human pathogen, Staphylococcus aureus, and other staphylococci. This agent blocks protein synthesis by interfering with the function of the ribosomal translocase, elongation factor G (EF-G). Unfortunately, the clinical efficacy of FA is being eroded by the growing prevalence of strains that carry the fusB determinant. Our current state of knowledge regarding FusB indicates that it represents a novel paradigm in antibiotic resistance, involving interaction with, and direct protection of, the drug target (EF-G). Furthermore, several lines of evidence suggest that FusB has not evolved as a FA-resistance protein, but actually represents a previously uncharacterized accessory factor active in prokaryotic protein translation. Consequently, it is of significant fundamental scientific interest. The mechanism by which FusB mediates its native role and resistance to FA remain poorly understood. Structural information will be essential to elucidate the mechanism of action of this resistance protein, but unfortunately neither FusB nor the FusB:EF-G complex have proven amenable to X-ray crystallography. In the current proposal, we intend to employ Nuclear Magnetic Resonance (NMR) spectroscopy to determine solution structures of FusB, and of a fragment of the EF-G protein with which it interacts, alone and in complex. In conjunction with experiments to precisely map key points of interaction between the two proteins, and to investigate the thermodynamics of the interaction, these studies will provide significant insights into FusB and its mechanism of action.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: INFECTION
Title: The chicken caecal microbiome: from baselines to biological impact
Funder: Biotechnology and Biological Sciences Research Council

Abstract: We propose to exploit the enormous opportunity offered by high throughput DNA sequencing (HTS) to make good the current deficit in knowledge of gut bacteria and their biological significance, in the chicken: the most important food animal exploited by humans. The intestinal microbiota play a central role in every aspect of alimentary tract function. Yet full scientific investigation of their composition and function has been thwarted by technical and logistic difficulties, both in culture-based conventional microbiology and in clone library approaches to phylogenetic analysis. HTS technology, while very cost effective in yielding very large amounts of information, is nevertheless not accessible without significant expenditure. We therefore propose first to undertake the crucial, but non-trivial, scoping experiments required to assess technical reproducibility and biological variability in the chicken caecal microbiome. We will use the classical approaches of experimental replication and statistical analysis to enable robust experimental design for subsequent studies. These will be the first such extensive baseline experiments to our knowledge in the emerging field of microbiomics based on HTS. We will then define the effects of fundamental variables in the life of a broiler chicken: through developmental change and growth, with dietary change to maturity, and in different host genetic backgrounds. In a key experiment relating to food safety, we will explore the effect of colonisation of the caeca with the most prevalent bacterial foodborne diarrhoeal pathogen, Campylobacter jejuni. Lastly we will probe the chicken caecal metagenome, to seek knowledge of the role of the microbiota in processing feed components such as complex plant-derived glycans. We believe this work will lay the foundation for a wide range of new research in the chicken, and on a wider front establish standards for future HTS-based microbiomics research.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: INFECTION
Title: Novel aptamer-based diagnostics and antiviral therapeutics for animal influenza viruses
Funder: Biotechnology and Biological Sciences Research Council

Abstract: The expression of a set of Avian Influenza virus proteins comprising haemagglutinin, and neuraminidase glycoproteins as well as the more conserved nucleoprotein (NP) and ion channel (M) proteins will provide target molecules against which DNA/RNA aptamers will be selected. The glycoproteins and proteins will be expressed in drosophila S2 cells yield well defined functional molecules that will be the targets for screening an aptamer library. Selection and counter-selection methods will be designed to yield molecules that exhibit defined strain and serotype specificity and the affinity and cross-reactivity determined using both surface plasmon resonance and agglutination inhibition assays. Aptamers showing suitable affinity and specificity will then be synthesised as 3' or 5' thiohexyl terminated derivatives for self-assembly onto gold nanoparticles (AuNP's) or gold electrodes. These conjugates will be the foundation for developing point of care diagnostic devices. Optical detection will be based upon the AuNP's forming a shell around the viral envelope with a resultant change in light scattering associated with the different size and structure of the virus coated with nanoparticles and the isolated nanoparticles. Electrochemical sensing will make use of redox labelled aptamers and the change in current associated with virus binding restructuring the aptamer and altering the distance between the label and electrode. High affinity aptamers isolated during library screening will also be evaluated in terms of their antiviral potential. Firstly, the antiviral properties of selected high affinity aptamers against selected H1N1 and H5N1 viruses in vitro through haemagglutination inhibition and neuraminidase inhibition assays and tissue culture virus infectivity assays. Those aptamers that prove most effective in the in vitro assays will then be evaluated for their protective effect in both a mammalian (mouse) and an avian (chicken) model of AI infection.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;5.1 PHARMACEUTICALS
Health categories: INFECTION