Development of critically needed new diagnostic tools for the WHO priority pathogen Lassa virus

The 2024/25 application process is now closed

Visit the MRC DTP/CASE at LSTM pages for further information.

Abstract

Lassa fever (LF), caused by the Lassa arenavirus (LASV), is a severe and often fatal viral haemorrhagic fever (VHF) and a major public health burden throughout West Africa, with an estimated tens of thousands of LASV infections and over 5,000 deaths annually. LASV has been designated as a pathogen with epidemic potential and a priority for research and development by WHO, including the development of new molecular and antigen based diagnostics.

The clinical course of LF varies from asymptomatic infection or non-specific febrile illnesses through to life-threatening conditions with bleeding, multi-organ failure and death. There is no approved vaccine for LF and although ribavirin is used for treatment, it is most effective when started in early disease, meaning that supportive care is critical in the management of these patients. Often the diagnosis is made too late, negating the benefit of ribavirin or other treatments.

The diagnosis of VHFs is complex, and tests are often only carried out in well-equipped reference laboratories, far removed from hospitals and clinics where patients first present. LSTM’s Diagnostics Group has been working with Global Access Diagnostics (GADx), a global leader in lateral flow test development, to develop tests for Crimean Congo haemorrhagic fever, and have demonstrated the utility of this approach for VHFs.

During this project we will develop point of care antigen based tests for LASV, and evaluate any new assays in Sierra Leone in collaboration with Kenema Government Hospital, and with partners in the Bernard Nocte institute & Nigeria. The antigen test will require target selection, protein expression in mammalian cell culture, antibody generation via multiple routes, and antibody triage/selection. Assays will then be prototyped at GADx’s state of the art manufacturing facilities. The project will require travel to Sierra Leone for field evaluations, and to other international collaborators for method development. During the project there will also be the opportunity for involvement in exploratory work to develop new molecular tools for LASV with various commercial partners.

This exciting project, across both the Department of Clinical Sciences and Tropical Disease Biology has the potential to deliver new diagnostics for this WHO priority pathogen and provide tangible translational outputs. The supervisory team includes, laboratory, clinical and commercial experience ensuring all aspects of the project are well covered.

Where does the project lie on the Translational Pathway?

T1 – Basic Research

Expected Outputs

This project will generate high quality publications in the field of LASV diagnostics, specifically on the design and evaluation of the diagnostic tests. This highly translational work will also aim to progress tests through the development pipeline to commercialisation. This work will complete a key aim of the 2019 WHO LASV R&D blueprint and therefore will be of international interest within the VHF community. 

 

We will encourage the student to use results obtained in this project as the foundation for early career fellowship applications from the Wellcome Trust and MRC and will assist with compiling these.

Training Opportunities
  • The student will receive training on a wide variety of laboratory techniques at LSTM, including mammalian cell culture, DNA cloning, protein expression systems, qPCR, DNA sequencing, and diagnostic test development.
  • Via working with our industrial partner GADx the student will receive training from a leading manufacturer of lateral flow tests, and will gain practical experience of antibody performance/binding kinetics assessment, and test prototyping.

 

  • Experience of working in LMIC laboratory settings will also be gained via our collaborations with the LASV reference centre in Sierra Leone, where the test evaluation will take place.
  • We will support the student in identifying and applying for external funding opportunities e.g. Bioinformatics courses

Skills Required

Skills in molecular biology, immunology or bioinformatics would be useful, but are not essential as training will be provided on all aspects of the project.

Key Publications associated with this project

Fraser, Alice J., Caitlin Greenland-Bews, Daniel Kelly, Christopher T. Williams, LSTM Diagnostics Group, Condor Steering Group, Richard Body, Emily R. Adams, Ana Cubas Atienzar, Thomas Edwards, David J. Allen. 2023. A high-resolution melt curve toolkit to identify lineage-defining SARS-CoV-2 mutations. Scientific Reports, 13: 3887

Atienzar, AIC et al., Accuracy of the Mologic COVID-19 rapid antigen test: a prospective multi-centre analytical and clinical evaluation. 2021. Wellcome Open Research. 6:132

Mazzola, L., Kelly-Cirino, K. Diagnostics for Lassa fever virus: a genetically diverse pathogen found in low-resource settings. 2019. BMJ Global Health. 4: 2

Siddle., K. et al., Genomic Analysis of Lassa Virus during an Increase in Cases in Nigeria in 2018. 2018. New England Journal of Medicine. 379:1745-1753