MRC CIC successful applicants 2020-21


PI Institution

Co-Is and institutions


Project Summary

Award Amount

Dr Emily Adams (LSTM)


Dr Tom Fletcher, Dr Joe Fitchett (Mologic, Bedfordshire), Dr Annelyse Duvoix (Mologic, Bedfordshire), Dr Ana Isabel Cubas Atienzar (LSTM), Prof Luis Cuevas (LSTM)

Development of monoclonal antibodies towards an antigen test for Crimean-Congo Haemorrhagic Fever

We aim to develop monoclonal antibodies that specifically bind with antigens of Crimean Congo Haemorrhagic Fever (CCHF) towards the development of an antigen detection test for CCHF.
The development of these antibodies is a crucial first step towards the development of rapid, lateral flow based antigen diagnostics. These will be developed as screening tests for rapid diagnosis at the point of care.

The antibodies will be developed by LSTM in collaboration with our commercial partner Mologic, a company leading the development of rapid diagnostics ( with a focus on low-resource settings with Public Health England.


Dr Martino Bardelli (Jenner, Oxford)

Jenner, Oxford

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

AAV-vectored delivery of engineered monoclonal antibodies as a prophylactic strategy against blood-stage malaria. 

A significant challenge in the development of malaria vaccines is the lack of effective antigen formulations that induce and maintain the very high concentrations of effective antibodies required to achieve protective immunity. Using long-lived potent monoclonal antibodies (mAbs) as prophylactics could provide an alternative route to accelerate malaria control and elimination programmes. Maximising mAb potency will be central to the success of this approach. We propose a proof-of-concept study that combines a proprietary antibody Fc-engineering platform with a vectored immunoprophylaxis (VIP) strategy to deliver previously characterised mAbs against two leading malaria targets (PfRH5 and PvDBP) to neutralise blood-stage Plasmodium parasites of humans.


Prof Giancarlo Biagini (LSTM)


Prof. Steve Ward, Dr Grant Hughes (LSTM), Dr Roger Hewson (PHE)

Defining the principles of a universal combination drug strategy against emerging viruses significant to human health

Proactive efforts towards the development of new antivirals will be essential to containing and eradicating future viral pandemics.  As part of pandemic preparedness efforts, it is therefore imperative that the a priori discovery and development of drugs, including new drug combinations, against viruses with pandemic potential is attempted.  Drug combination strategies offer a number of advantages to monotherapies including the potential to achieve greater efficacy, the potential to increase the therapeutic index of drugs and the potential to reduce the emergence of drug resistance.  We have recently shown that the combination of Remdesivir (RDV)-Ivermectin (IVM) results in a synergistic interaction with improved in vitro antiviral activity against SARS-CoV-2.  We hypothesise that the mechanism underpinning the synergistic interaction is translatable to other important viral pathogens, notably RNA viruses, including important arboviruses.  In this study we propose to test this hypothesis and determine whether RDV and related C-adenosine nucleoside analogs have a synergistic antiviral effect when combined with known RNA polymerase inhibitors against important emerging viruses including Rift Valley fever (RVF), Zika (ZIKV), Chikungunya (CHIKV) and tick-borne encephalitis (TBEV) viruses.  We anticipate that the data established in this study will form the basis of future drug combination discovery and development programmes for global pandemic preparedness.


Dr Laura Bonney (Afrough) (PHE)


Prof. Krzysztof Koziol (Cranfield University), Dr. Alex Skordos (Cranfield University), Prof. Roger Hewson (PHE)

ViXrayCines (Virus X-ray vaccines): High throughput virus inactivation by X-rays for rapid vaccine and reagent production

X-ray inactivation enables the efficient production of high-fidelity viral nucleic acid and antigens for use in a multitude of downstream detection and functional assays, including the production of vaccine candidates. To meet broad application demand, we propose a scaling solution to significantly increase production capacity by developing a bespoke continuous microfluidic flow system. This will allow 5-fold recovery of inactivated virus in a matter of minutes, which is currently the major hurdle in X-ray technology use for viral inactivation at scale. This scaling procedure would be relevant to a range of emerging zoonotic viruses, including ACDP 3 & 4 pathogens.


Dr Michael Delves (LSHTM)


Prof Matthew Fuchter (Imperial College), Dr Javier Gamo (Glaxosmithkline)

Hit-to-lead optimisation of DDD01034957 as a novel antimalarial

DDD01034957 is a molecule with antimalarial properties that possesses a chemical scaffold unique from all other antimalarials currently under development. Initial study has revealed this hit molecule to be fast acting and active against many drug resistant parasite strains. We propose a hit-to-lead programme to optimise the activity and pharmacokinetic properties of DDD01034957 to support the onward application for an MRC DPFS award.


Prof Simon Draper (Jenner, Oxford)

Jenner, Oxford

Dr Rob Moon (London School of Hygiene and Tropical Medicine), Dr Lloyd King (Jenner Institute, University of Oxford), Dr Jee-Sun Cho (Jenner Institute, University of Oxford)

Development of a next-generation Plasmodium vivax vaccine for Blood-Stage Malaria

The identification and assessment of novel Plasmodium vivax vaccine antigens, is a significant challenge due to a lack of in vitro culture systems for testing vaccine efficacy for this human parasite. To overcome this, we developed a novel assay platform to screen vaccine-induced functional antibodies, using culture adapted P. knowlesi parasites, modified to express P. vivax candidate vaccine antigens. This powerful new system will be used to investigate the potential of the PvEBP antigen as a next-generation vaccine candidate for P. vivax. PvEBP binds reticulocytes, is conserved and naturally-acquired antibodies to this antigen strongly correlate with protection against clinical malaria.


Dr Thomas Edwards (LSTM)


Emily Adams, Lisa Baldwin, Luis Cuevas (LSTM). Antonia Sagona (University of Warwick), Jenifer Mason (Liverpool University Hospital Foundation Trust), Mark Sutton (Public Health England)

Recombinant bacteriophages for direct detection of bacterial blood stream infections

Rapid detection of bacterial pathogens directly from blood remains one of the greatest challenges in diagnostic microbiology. Current strategies rely on blood culture, which takes 24-48 hours, and identifying drug resistance requires further phenotypic tests, delaying targeted therapy and the overuse of empirical antibiotics. Alternative molecular techniques are usually insufficiently sensitive.
We propose to use recombinant fluorescent bacteriophages to provide a signal for the detection of bacteria directly from blood. This approach can rapidly detect low concentrations of bacteria, enable AMR detection,  and by skipping the culture step, provide same day diagnosis.


Dr Rosemary Lees (LSTM)


Bart Kahr, Michael D. Ward (New York University), Jessica Williams, Hilary Ranson (LSTM)

Can a simple change of crystallisation state restore or enhance the efficacy of pyrethroid insecticides for vector control?

Contact adulticides kill infectious disease vectors at the interface between a crystalline particle and mosquito tarsi. Recently the pyrethroid insecticide deltamethrin was shown to be 12 times more bioavailable when formulated as a second crystalline structure (polymorph) not previously identified, against an insecticide-susceptible Anopheles species from the USA. African malaria vectors have developed multiple pyrethroid resistance mechanisms, including barriers to penetration.  This project will address a key milestone in the translation from proof of concept to new insecticide formulations by evaluating the bioefficacy and rate of penetration of crystalline forms of public health insecticides against African malaria vector populations.


Dr Kirsty McHugh (Jenner, Oxford)

Jenner, Oxford

Prof Richard J Pleass (LSTM), Dr Martino Bardelli (Biochemistry Department, University of Oxford)

Avidity engineering to improve mAb therapeutics for emerging viral infections

Monoclonal antibodies (mAbs) offer a promising therapeutic option to control emerging viral infections. MAb deployment for infectious diseases remains limited, with the main drawback stemming from the in vivo levels required to achieve protection – mAb potency drives the need for high dosage leading to high cost per dose and burden of supply. We propose to exemplify a mAb engineering platform technology that substantially improves mAb potency to two prototype viruses – SARS-CoV-2 and Ebola virus. By lowering the effective dose, our strategy will have a significant impact on the ability to administer mAbs as therapeutics on a large scale, making mAb-based drugs a more cost-efficient option.


Dr Anita Milicic (Jenner, Oxford)

Jenner, Oxford

Prof. Adrian Hill, the Jenner Institute, NDM, Oxford, Prof. Eleanor Stride, IBME, Dept. of Engineering, Oxford

In vivo evaluation of a single-dose malaria vaccine delivered inside microfluidics-generated polymer microcapsules

Single‐dose immunisation would circumvent many of the challenges facing global vaccination coverage, and has been a long‐standing ambition in vaccine development. It involves the booster dose being encapsulated for a delayed in vivo release and administered together with the first (priming) vaccine. Using a novel microfluidcs‐based system we have manufactured microcapsules that contain a model antigen, and demonstrated delayed burst release in vitro after 4 weeks. This project will test the encapsulated antigen in mice, with the aim to demonstrate successful vaccine delivery in vivo following encapsulation. Single‐dose immunisation will be applied to our leading viral vectored malaria vaccines.


Dr Robert Moon (LSHTM)


Colin Sutherland (LSHTM); Paul Bowyer (NIBSC)

Antigen orthologue replacement: Development of species-specific reference panels for evaluation of malaria rapid diagnostic tests.

Rapid diagnostic tests (RDTs) are widely used for malaria diagnosis, and in many settings are the only available laboratory test. RDT often deploy pan-specific monoclonal antibodies against parasite LDH to identify all malaria species, but test performance is highly variable for  Plasmodium ovale curtisi and P. ovale wallikeri. Systematic evaluation of new and existing RDT is hampered by lack of WHO international reference standards for these species. This proposal will generate a panel of transgenic P. knowlesi parasites expressing PoLDH antigen variants as a renewable resource for assessment of RDT performance and development of new test antigens.


Dr Ian Passmore (LSHTM)


Brendan Wren (LSHTM), John Heap (University of Nottingham)

High-throughput Stop-Start DNA assembly pipeline for affordable glycoconjugate vaccines against Group B Streptococcus infection

Glycoconjugate vaccines are one of humanity’s most successful innovations. However, the complexity of processes required to produce glycoconjugate vaccines is expensive, which has limited their widespread development and utilisation. We will apply a novel synthetic biology approach to develop a rapid and efficient method for engineering recombinant glycoconjugate vaccines in bacteria. We will apply the principles of multi-part DNA assembly to engineer the glycan biosynthetic pathway of the Group B Streptococcus (GBS) capsular polysaccharide, which will be utilised as a component in an affordable, reliable supply of vaccine against GBS infection.


Prof Jayne Sutherland (LSHTM)


Prof Graham Ball (Intelligent OMICS & Nottingham University)

Optimisation of a host biosignature in sputum for development of a rapid lateral flow test for tuberculosis

Tuberculosis (TB) is still a major global health problem with 1.5 million deaths per year, which is likely to increase due to the effects of SARS-CoV-2 on access to testing and treatment. We have identified and patented a biosignature comprised of host markers in sputum samples which meets the WHO product profile for a Triage test for TB. With CiC funding, we aim to optimise this signature, determine its global applicability, and for identifying treatment response. If successful we will apply for follow-on funding for development of a rapid, lateral flow-based triage test for TB for use in basic health clinics.


Dr Joseph Turner (LSTM)


Giancarlo Biagini, LSTM.  Andrew Owen, James Stewart, University of Liverpool

A humanised mouse model of CoV2 respiratory disease for therapeutics development

We have recently established a humanised mouse model of SARS-CoV2 (K18-hACE2 mice) that exhibits sustained viral replication and acute respiratory pathology, with poor survival outcome dependent on inoculate dose. This project will characterise the inflammatory cell and cytokine milieu both in the lung microenvironment and systemically following infection. We will determine whether repurposed anti-viral therapies with or without combined anti-inflammatory treatment (e.g. dexamethasone) can modify viral titre or lung disease. Further, we will comparatively test experimental COVID combination therapies identified in the LSTM/UoL preclinical screening pipeline for their ability to perturb viral load and/or lung hyper-inflammation in humanised ACE2 mice.


Dr Nadina Wand (PHE)


Professor Roger Hewson (PHE)

Rapid portable isothermal detection of Crimean-Congo Haemorrhagic Fever Virus infection using a novel CRISPR nucleic acid diagnostic method, SHERLOCK

Development of rapid point-of-care diagnostic tools for the detection of Crimean-Congo Haemorrhagic fever virus in patient samples is identified as a priority in the WHO R&D CCHF roadmap for the prevention and control of this high-consequence pathogen in affected countries. We propose to apply a CRISPR-enzyme based diagnostic approach, SHERLOCK, in conjunction with our previously developed RPA assay, to detect CCHF nucleic acid, resulting in a highly sensitive assay appropriate for low-resource settings or a mobile field laboratory in remote regions, where disease burden is most significant and rapid results can lead to important gains in patient management.


Prof Steve Ward (LSTM)


Prof P. M. O’Neill (University of Liverpool), Dr W. D. Hong (University of Liverpool), Dr S. Leung (University of Liverpool) and Dr D. Soldati-Favre (University of Geneva)

Optimisation of the Antimalarial and DMPK Properties of A Series of Plasmepsin IX/X Beta-hydroxyethylamine Based Inhibitors.

Plasmepsin IX and X are aspartic proteases that play crucial roles in erythrocyte invasion and egress of the malarial parasite. Targeting these enzymes can effect both treatment and chemoprotection against malaria infection. An early lead series of beta-hydroxyethylamines that targets plasmepsin IX/X, demonstrates potent antimalarial activity in vitro and in vivo, but sub-optimal DMPK properties restricting the progression of the series. This project sets out to demonstrate that key DMPK characteristics of this series can be optimised, whilst maintaining the antimalarial activity and the selectivity against plasmepsin IX/X(over other plasmepsins), as a rationale for onward development


Prof Hilary Ranson (LSTM)


Iris Wagner, University of Liverpool, Rob Beynon, University of Liverpool, Linda Grigoraki, LSTM, Antoine Sanou, CNRFP

The application of mass spectrometric approaches to rapidly and accurately age diverse mosquito populations.

A method that provides a rapid assessment of mosquito age, that is robust to both changes in the environment the mosquitoes have been exposed to and to storage conditions post capture would greatly accelerate the evaluation of mosquito control strategies. Our preliminary data using rapid evaporative ionisation mass spectrometry (REIMS) suggests this method may surpass all other current approaches in both ease of application and accuracy of results.  Here we propose essential further validation steps; if successful, this potentially transformative technology will lead to multiple follow-on projects to evaluate the impact of vector control strategies.


Dr Nicholas Furnham (LSHTM)


David Allen (LSHTM)

Experimental validation and hit-­to-­lead advancement of Mpro inhibitors for treatment of SARS-­CoV-­2

SARS-­CoV-­2 has established itself as a new endemic disease requiring a combination of vaccination and drug treatments for its long term control. The SARS-­CoV-­2 Mpro enzyme is widely considered a prime target for drug intervention. The goal of this project is to demonstrate the effectiveness, in cellulo, of new potent inhibitors of Mpro. By delivering new compounds with proof of efficacy, a strong basis for the mechanism of action and a route to highpotency we expect to have a set of key chemical assets to further clinical research and ultimately new drug treatments.


Dr Stuart Dowall (PHE)


Roger Hewson (PHE), Robert Possee (Oxford Expression Technologies Ltd)

Advanced testing of an ELISA diagnostic test for Crimean-Congo Haemorrhagic Fever virus

Crimean-Congo Haemorrhagic Fever virus (CCHFV) is a highly contagious pathogen responsible for severe disease. It is primarily transmitted to humans by ticks. The viremic period is brief, making its direct detection by PCR of limited value as patients often present after virus has been cleared. Thus, diagnosis commonly relies on serological assays to detect specific CCHFV antibodies. PHE developed an ELISA based on recombinant CCHFV nucleoprotein, and this has been developed into a kit format. To ensure the assay is fit-for-purchase, beta-testing is required to gather feedback from potential end users and progress the kit to CE-marking.


Prof Adrian Hill (Jenner, Oxford)

Jenner, Oxford

Dr. Ahmed M. Salman, Jenner Institute, University of Oxford.

Generation and assessment of full-length spike (S) protein and receptor-binding domain (RBD) fused to HBsAg as virus-like particle (VLP) vaccine candidates for durable protection against SARS-CoV-2

COVID-19 outbreak has posed a serious threat to global public health which calls for the urgent development of safe and effective vaccines [1]. The S protein mediates viral entry into host cells by first binding to a host receptor. By blocking the attachment of SARS-CoV-2 RBD to ACE2-expressing cells, thus inhibiting their infection to host cells, SARS-CoV-2 RBD-specific antibodies neutralize SARS-CoV-2, suggesting the potential to develop SARS-CoV-2 RBD-based vaccines for prevention of SARS-CoV-2 infection. Therefore, the RBD in SARS-CoV-2 S protein is now an established target for the development of virus neutralizing antibodies, and is an excellent target antigen for vaccines [1]. In this project, we will build on our unique experience of using virus-like particles (VLPs) with saponin adjuvant in malaria to phase III trials to now induce high-level durable antibody responses against the full-length SARS-CoV-2 spike (S) protein or the RBD alone fused to HBsAg.