MRC CIC successful applications Round 3 - 2025

Anita Milicic

Oxford

Eleanor Stride, Romain Guyon, University of Oxford

Enhancing breadth and durability of protection against future SARS-CoV-2 variants via a novel sustained release vaccine formulation

Commercially Sensitive

£44,221.39

Daniel O'Connor

Oxford

Barbara Camanzi, Hartree Centre STFC

Developing synthetic cohorts for in silico vaccine trials

Vaccine development is a lengthy and expensive process, with only a tiny percentage of candidates completing the entire developmental pathway to licensure. The high risk of failure compounds costs, discouraging the investment that is required to maximise the advancement of impactful vaccines. This is particularly problematic for tropical infectious diseases that effect countries with limited purchasing power. Novel approaches to reduce the cost and time associated with vaccine development are critical. This proposal will provide data of the viability of using generative modelling techniques to produce synthetic cohorts, representative of vaccine target populations (e.g., paediatrics) to perform in silico trials.

£52,148.73

Andre Furger

Oxford

Dr Kirsty McHugh, Department of Biochemistry, University of Oxford. Prof Richard J Pleass, LSTM.

mRNA delivery of monoclonal antibodies as a prophylactic strategy against blood-stage malaria.

Monoclonal antibodies (mAbs) offer a promising therapeutic option to combat malaria. The use of therapeutic mAbs for infectious disease has been limited due to cost, scale-up and supply chain limitations. Maximising mAb potency and exploring delivery approaches that provide cost-effective alternatives to passive transfer of mAbs are central to the success for malaria prophylaxis. The production of mAbs via mRNA offers a cost-effective alternative to existing protein-based methods. This application proposes to test whether mRNA delivery of anti-malarial mAbs, with and without Fc-engineered multimerisation mutations, can achieve high level and durable expression using the AAV-delivery strategy as a benchmark.

£38,993.93

Isabelle Dietrich

Pirbright

Eva Perez, Jonas Albarnaz, Steven Fiddaman, The Pirbright Institute. Adrian Smith, University of Oxford.

Development of a comparative genomics and functional pipeline for livestock interferons as prophylaxis and treatment option for livestock viral diseases.

Viral diseases of livestock pose a significant global burden on animal and human health, livelihoods, economies, and societies. For many of them vaccines and specific treatments are critically lacking.

This project will develop a comparative genomics and functional pipeline for the use of livestock interferons as vaccine adjuvants and emergency antiviral treatments. Livestock genome and transcriptome data will be analysed to map interferon expression landscapes. Interferon sequences will be collated into a community-accessible expression plasmid library, and selected interferons tested for antiviral and immunomodulatory properties. The establishment of sequence-function relationships will allow the selection of candidate interferons for veterinary use.

£45,321.96

Young Chan Kim

Oxford

Professor John Kelly, Professor of Molecular Biology. Department of Infection Biology, London School of Hygiene and Tropical Medicine. Professor Sir Andrew Pollard, Ashall Professor of Infection & Immunity, and Honorary Consultant Paediatrician. Director of the Oxford Vaccine Group. Emil Joseph Vergara, Postdoctoral researcher, Oxford Vaccine Group (OVG), University of Oxford.

Evaluation of the efficacy of an mRNA-based multi-antigen vaccine in a highly sensitive bioluminescence mouse model of chronic Trypanosoma cruzi infection

Chagas disease, caused by Trypanosoma cruzi infection, leads to progressive cardiovascular and intestinal pathologies due to parasite persistence in affected tissues. Drug therapy for chronic Chagas disease offers limited efficacy and a myriad of side effects. A prophylactic vaccine that can halt parasite persistence can prevent clinical sequelae associated with chronic infection. Previously, we developed viral-vectored and mRNA Chagas vaccines which provided 100% protection in the mouse model of acute T. cruzi infection. In this project, we will test a mRNA Chagas vaccine in a highly sensitive bioluminescent mouse model of chronic T. cruzi infection. We will test a combination mRNA Chagas vaccine targeting both extracellular and intracellular forms of the parasite for its potential to enhance protection.

£45,915.43

Richard Wall

LSHTM

None at this stage.

Drug target identification of promising compounds active against Mycobacterium tuberculosis

There is an urgent need for new drugs with novel molecular targets for the treatment of tuberculosis. Our industrial partner, Janssen, has recently completed a high-throughput whole cell screen against Mycobacterium tuberculosis identifying multiple potent, phenotypically active hit compounds. However, development of these compounds is currently hindered by a lack of validated drug targets. This project will perform target identification studies on the most potent and chemically tractable of these compounds and develop a toolbox of genetic tools to support further medicinal chemistry programmes. Ultimately, this project will facilitate future grant applications and enhance collaboration between the project partners.

£46,628.36

Serge Mostowy

LSHTM

Dr Richard J. Wall, Infection Biology, LSHTM

Leveraging a Mycobacterium marinum-zebrafish infection model to identify tuberculosis treatment combinations

Tuberculosis (TB) remains a leading cause of death by an infectious disease, further exacerbated by the rise in drug-resistant infections. The long treatment duration, together with drug toxicity and resistance, highlights an urgent need for shorter, more tolerable regimens. Murine models have traditionally guided TB regimen selection, but limitations, including the high number of possible combinations, prompt the development of alternative strategies for identifying new regimens. Here, we aim to establish a Mycobacterium marinum-zebrafish infection model, leveraging the high-throughput, cost-effective drug screening capabilities, to accelerate the discovery of new drug combinations, reduce dependence on murine models, and improve treatment outcomes.

£46,234.60

Laura-Oana Albulescu

LSTM

Prof. Nicholas Casewell, LSTM. Prof. Paul O’Neill, University of Liverpool

Defining lead candidate drug combinations as new therapeutics for snakebite envenoming

Snakebite is a medical emergency causing ~100,000 deaths/year. Small molecule inhibitors are currently in clinical trials, but the number of lead candidates remains low (n=3) and the potential for attrition high. Further, drug combinations are likely necessary to provide sufficient neutralising breadth against geographically diverse snakes, yet none are in clinical development. Here we will leverage our prior medicinal chemistry lead optimisation work to determine the optimal drug combination from five lead candidate oral drugs that target one of two major venom toxin families. Delivery of a lead candidate drug combination will accelerate future translation of oral snakebite therapies as first-line interventions and circumvent existing IP barriers.

£43,629.70

Mark Paine

LSTM

Prof Sheila Sedeghi, University of Torino. Amy Guy, LSTM/LITE

Developing a mosquito microfluidic immobilized enzyme reactor (μ-IMER) to accelerate insecticide discovery

Insecticides are key to the control of insect-borne disease, but the rapid evolution of resistance is a constant threat to disease control programmes. There is a pressing need to develop efficient predictive tools to identify metabolic vulnerabilities to streamline insecticide discovery and reduce the time and costs in the development pipeline. Our aim is to design microfluidic immobilized enzyme reactors to predict the metabolic fate of insecticides in mosquitoes. This will provide early information on the metabolism and resistance liabilities of new insecticide candidates to accelerate production of effective mosquito control products.

£36,468.80

Emma Kennedy

UKHSA

Dr Stuart Dowall, UKHSA. Prof Roger Hewson, LSHTM.

Function and efficacy of humanised anti-CCHFV glycoprotein antibodies.

UKHSA have successfully developed humanised monoclonal antibodies (HMAb) to Crimean-Congo Haemorrhagic Fever Virus (CCHFV) envelope glycoprotein antigens as positive controls for serological assays. We have demonstrated their specificity to either the Gc or Gn glycoprotein and are seeking funding to take this further by investigating the functional and protective properties of each antibody. This study will determine the neutralising activity alongside taking the most promising clones forward to determine their efficacy potential in a CCHFV challenge model in mice as the first stage in evaluating therapeutic development of these HMAb candidates.

£92,064.00