Development of point-of-care testing for Lassa and other hemorrhagic fever arenaviruses

Project Summary/Abstract Emerging infectious diseases pose a significant risk to human health. Among emerging pathogens, hemorrhagic fever viruses (HFVs) pose the greatest risk in terms of the potential for morbidity and mortality. These viruses are endemic in remote regions, produce large outbreaks that display high mortality rates, and have a high potential become pandemics. One of the largest families of HFVs is the Arenaviruses, which includes 6 DHHS select agents. The most well-known of these, Lassa virus, has caused an increasing number of infections in recent years, including a 2018 outbreak in Nigeria that led to over 100 deaths. In 2017, the World health Organization designated Lassa virus as a priority pathogen for R&D efforts due to its potential to generate a public health emergency. Other hemorrhagic fever arenaviruses, including Lujo, Chapare, Guanarito, Junin, and Machupo represent an increasing source of concern based on their increased distribution and recent instances of human-to-human transmission. Current diagnostic capabilities for Lassa virus and other arenaviruses are extremely limited, especially in the case of point-of-care (POC) diagnostic assays. Here, we propose to develop a POC diagnostic assay with the sensitivity and breadth of coverage required to diagnose Lassa virus infections currently present in West Africa. In addition, we will generate single chain antibody phage display libraries, broadly reactive high affinity diagnostic antibody pairs, a prototype assay chips for the 5 other arenaviruses that are Category A Priority Pathogens. We have previously used these procedures to develop a POC diagnostic assay for Ebola virus that displays a sensitivity better than the current gold standard, PCR. The successful completion of these studies will result in the first POC diagnostic assay that is capable of detecting all Lassa strains of clinical importance and a panel of high affinity diagnostic Abs and assays for all Category A Arenaviruses. In addition, the broadly reactive single chain antibody libraries we produce could be used to rapidly generate diagnostic antibodies against novel arenaviruses that arise as zoonotic outbreaks. This work will thus significantly improve our preparedness for almost any future major Arenavirus outbreak with pandemic potential.