Community Research and Development Information Service - CORDIS

H2020

IF-EBOla Report Summary

Project ID: 666102
Funded under: H2020-EU.3.1.

Periodic Reporting for period 2 - IF-EBOla (Control of the Ebola Oubreak by both innovative Ultrasensitive Detection of EBOV and therapy)

Reporting period: 2015-11-01 to 2016-10-31

Summary of the context and overall objectives of the project

Our proposal was designed from the outset to rapidly respond to control the EBOV outbreak from spreading in West Africa. The work plan involved two of the primary EVD outbreak sites, Sierra Leone and Guinea. Physicians, public health authorities and outbreak experts worked on site, under ethical approval, and collaborated with companies and institutions to form a seamless consortium of outstanding complementary partners, all sharing their innovative technological approaches for a common goal. During this last period, the IF-EBOLA program encountered challenges, partly due to the unexpected rapid decline in the epidemic, which didn’t allow for realization of the initial project goals. In addition, changes in the approval process and requirements made it impossible to ship samples out of country for analysis in a timely fashion, which led to the loss of an extremely valuable resource. Therefore, during this period the consortium generated limited preliminary data. The impact of the changing landscape, both political and infectious, on the IF-EBOLA program during the 2nd Period and methods for mitigating this unexpected new reality in West Africa are described below.

The IF-EBOLA consortium developed strategies to mitigate the issues and successfully address requirements for completion of the project. In addition, during this period the consortium achieved significant preliminary results, which if confirmed, will make the IF–EBOLA action a great European success story. Given the primary goal of the project, to dramatically increase an Ebolavirus patient’s survival (“An early Ebola virus detection for an early passive immunotherapy”), all objectives, constituting the main pillars of the project, have successfully passed proof of concept. Thus, equine antibodies demonstrated capacity to neutralize Ebolavirus in vitro and in vivo with 100% survival of Ebolavirus infected mice. In addition, at Kenema Hospital (KGH), Sierra Leone, we were able to increase by more that 100-fold the sensitivity of Ebolavirus detection (from clinical samples) using our ApoH-sample preparation method coupled with the USAMRIID FDA-approved Ebolavirus PCR based diagnostic, which was employed during the outbreak at KGH. In addition, the ApoH-sample pretreatment technology enabled an extremely large increase in Ebolavirus reads generated by NGS of samples as compared with direct NGS without ApoH pretreatment, providing very accurate sequence analyses of Ebolavirus quasi-species that circulate in a patient or cohort. Furthermore, with the “Rigel” Algorithm for NGS, metagenomic analysis revealed 18% Lassa virus (a confounding factor) among existing sequence reads. Finally, human monoclonal neutralizing antibodies were isolated that targeted several Ebolavirus proteins from a Sierra Leone convalescent survivor, which exhibited neutralizing activity against Zaire ebolavirus. All of these results are detailed in the comprehensive report.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Modified and updated activities for IF-Ebola:

Despite the major challenges described above the IF-EBOLA consortium has mitigated these with the following solutions:
1. In WP2, the objective was to test purified equine anti-EBOV polyclonal F(ab’)2 in a clinical trial under field conditions. However, by the time the antiserum was developed and ready for testing the outbreak had decline and it was no longer feasible to perform the scheduled clinical trial. Instead, we focused on fine-tuning the anti-EBOV polyclonal F(ab’)2, and investigated performance of further experiments in animal models in WP2. The anti-EBOV polyclonal F(ab’)2 performed successfully in a murine model and additional studies, first in guinea pigs and then NHPs, will be undertaken in the next period.
2. WP3 had two objectives: 1) to provide lab support for the clinical trial planned in WP4 (which was no longer applicable), and 2) to provide blood samples from Ebola patients for validation of the diagnostic under development (in WP5) and research on the human immune response to Ebola infection (WP5). However, the project was unable to get permission to export samples from Sierra Leone in a timely fashion. As such, all sample-dependent tasks in WP3 and WP5 have been delayed. During this period, however, we performed experiments that were not dependent on these samples, outlined below, and additionally, we tried to secure access to Ebola blood samples from other countries. This issue has been resolved, samples are now being retrieved from Liberia, and the scheduled tasks will be pursued in the next RP. In addition, with the help of Leslie Lobel (consultant for ClinicalRM) and John Dye (USAMRIID), we have access to hot samples too.

Major milestones reached during this Reporting Period:

1. Treatment: As mentioned above, the post-exposure passive anti-Ebolavirus immunotherapy approach using the anti-EBOV polyclonal F(ab’)2 performed extremely successfully in a sharp experimental murine model of Ebola infection.
2. Diagnostic: Among the activities performed in Sierra Leone in February 2016, IRD generated significant preliminary data demonstrating successful serological capture and concentration of Ebolavirus with ApoH, increasing sensitivity between 1 to 2 logs as compared with RT-PCR alone (the current FDA approved USAMRIID method, used in country from the beginning of the Ebola outbreak in 2014).
3. Immune-profiling: BGU demonstrated that an EVD survivor, infected in Sierra Leone, had specific humoral and cellular EBOV Zaire/Makona immune responses. Moreover, this patient’s antibodies were able to neutralize, to a lesser extent, other Ebolavirus strains including Bundibugyo and Sudan. This will facilitate optimization of antigens for immunization or for serological diagnostics and isolation of broadly neutralizing human monoclonal antibodies for treatment.
4. Metagenomic analyses: using the extremely powerful and unique RIGEL algorithm, OIB generated outstanding data demonstrating that 15% of samples from West African Ebolavirus patients, which had Ebola sequence reads by NGS, contained Lassa sequences too. Based upon NGS-metagenomic analyses, optimized probes were designed to improve specificity of Ebola detection and co-infections using PCR or other pathogen detection systems including field deployable nanosensor array isothermal amplification. In addition, when using the ApoH sample preparation methodology, we dramatically increased the efficacy of NGS reads by increasing their number by 300 to 400% as compared with NGS read numbers yielded in the absence of the ApoH method. Finally, these analyses will enhance and complement those from our immune profiling studies.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The development of Fab’entech anti-Ebola polyclonal Immunoglobulin is among the few potential treatments officially identified and supported by the international community, in particular WHO and EMA. Such a project will accelerate the demonstration of the product interest and efficacy and then support the development of the company by offering the product to WHO/United nations for the low income countries, as well as a treatment for exposed personnel such as health care workers, army, NGOs, civilians etc… This study will support additional procurement of the products by governments as well as NGO institutions, and private institutions.

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