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Control of the Ebola Oubreak by both innovative Ultrasensitive Detection of EBOV and therapy

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A new era in Ebola diagnosis and treatment

Ebola virus (EBOV) disease is a haemorrhagic fever that can be fatal if left untreated. The 2014 outbreak in West Africa reached historic proportions and spread rapidly beyond Africa, emphasising the lack of ultrasensitive diagnostics as well as efficient drugs against EBOV.

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Currently, there are no vaccines or antiviral drugs approved for prevention or treatment of EBOV. As it can be transmitted to humans from infected animals, there is an imminent need for prompt diagnosis and protection strategies in EBOV endemic regions. In addition, better understanding of survival and pathology factors is critical for the design of appropriate countermeasures. The EU-funded IF-EBOLA project was a collaborative effort among European and African partners designed to control EBOV spreading during an outbreak. The key objective was to “set up both practical and fundamental countermeasure strategies required for efficient preparedness by the local African public health authorities to control future Ebola outbreaks,″ explains project co-ordinator Prof. Veas. “Our philosophy was to combine an early passive anti-Ebola immunotherapy prompted by timely EBOV-diagnosis, along with immune response monitoring in survivors,″ he continues. The consortium developed different innovative technological tools including methods for the ultrasensitive detection of Ebola virus alongside a polyclonal antibody targeting EBOV designed to be preferentially used on early-diagnosed Ebola patients to improve their prognosis. Additionally, researchers performed accurate monitoring of the efficiency of immune response in EBOV disease survivors to achieve a better understanding of survival factors and design novel therapies and vaccine approaches. A novel integrated approach for tackling EBOV Undoubtedly, EBOV detection must take place during the early phase of the disease, when pathogen load is low and symptoms fairly mild, to apply supportive and specific treatment as soon as possible. However, it is equally important to treat convalescent patients who are asymptomatic but can still transmit the disease. IF-EBOLA used a magnetic-bead sample enrichment preparation approach to capture virus in patient samples. Combined with a real-time PCR method, scientists achieved ultrasensitive EBOV detection, sensitive enough to reveal the presence of residual EBOV from self-cured convalescents who had a previous acute infection. The anti-EBOV antibody preparation exhibited, as expected, good pharmacological characteristics such as lack of toxicity, good stability and bioavailability, as well as high anti-viral potency both in vitro and in vivo. When tested in different animal models of the disease, the antibody demonstrated a strong capacity to improve the virus-associated pathophysiology, and an important increase of survival rates close to 100 %. Future therapies depend on virus diversity To better understand the immune response against Ebola before and after treatment, emphasis was given to the characterisation of various immune and infectious parameters alongside EBOV diversity. State-of-the-art technologies were used such as next generation sequencing, metagenomics and DNA arrays. Metagenomic analysis of banked samples collected from patients infected with Ebola virus in west Africa revealed a prevalence of 18 % of Lassa virus alongside nosocomial bacteria and current local infections such as HIV, Mycobacterium tuberculosis and malaria. The novel integration of genomics and computational tools helped generate a reference database of unknown emerging and re-emerging pathogens that will be consulted for protection against pathogen diffusion. Intriguingly, the majority of EBOV strains isolated in Sierra Leone demonstrated a rapid change as the virus passes from patient to patient and even when it persists within a single patient. This is of vital importance as mutations could eventually affect disease diagnosis, vaccines and potential treatment selection. Collectively, from a rational designed preparedness strategy the European-USA consortium of the IF-EBOLA action produced interesting data from collected-banked samples (with Sierra Leone and Liberia MoH partners) and outstanding tools to overcome unmet needs such as ultrasensitive detection of ultra-low viral loads, a highly efficient antibody-dependent therapy able to rescue ebolavirus-challenged animals from death. Importantly, EBOV evolution data and co-infections as well as protective immune responses in survivors must be considered for future patient management alongside the development of additional countermeasures to achieve optimal therapeutic results.

Keywords

IF-EBOLA, Ebola virus (EBOV), antibody, outbreak, ultrasensitive diagnostic, survivor-protective immune response

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