The development of a rapid diagnostic test for Ebola virus.

点击翻译按钮获取中文摘要

The 2014-15 Ebola in West Africa outbreak exposed the world's vulnerabilities to infectious diseases and today Ebola remains at the top of the WHO list for priority pathogens with high epidemic potential and remaining need for R&D. Specifically, there is still an urgent need for rapid diagnostic tests as current tools lack the sensitivity, specificity to detect pan-Ebola species and data connectivity to support decentralised testing. The aim of this PhD project is to build a new generation of rapid, low cost and easy to operate diagnostic test for early diagnosis of Ebola virus disease (EVD), with the ability to detect different viral species, in decentralised resource-poor settings. This project will be based on a formally established collaboration between McKendry's group at LCN and Dye's group at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID). This project builds on a major breakthrough by Dr Dye published in the journal "Cell" which screened 349 monoclonal antibodies from human survivors and identified lead candidates which can specifically identify pan-Ebola species, targeting the inter-promoter epitope in the GP fusion loop, a critical and conserved element of the viral membrane fusion machinery. For this project Dr Dye will share his in-house production of unique monoclonal antibodies against Ebolavirus and Marburgvirus with high specificity and sensitivity to identify specific viral proteins. Characterisation of these Capture antibodies and their conjugation to nanoparticles will be performed using ELISA and Biolayer-Interferometry. Then, the characterized antibodies will be used for the development of multiple target analyte lateral flow test strip for the detection and differentiation of Ebola virus strains, including Sudan virus, Zaire virus and Bundibgyo virus. This test strip will be comprised of multiple test lines and modified nanoparticles for calorimetric result readout. Then, the assay will be calibrated and the limit of detection will be determined using recombinant viral proteins. Finally, emerging infections rank at the top of over Cabinet Office Risk Register, alongside threats such as terrorism. Moreover, this project proposal strongly aligns to UKRI, GCRF, NIHR, UN and WHO priorities for rapid diagnostic tests for infectious diseases and emergency preparedness. Hence, successful development of this rapid tests for acute Ebola infections could contribute to major human and economic benefits to patients and populations worldwide