CIHR Innovative Ebola Operating Grant – Success stories

The years 2014-2016 were marked by the most devastating Ebola outbreak ever experienced by the international community. The focus of our team during the epidemic was divided on two fronts. On one side, we were assisting the World Health Organization and Médecins Sans Frontières by offering diagnostic services directly in the field, through rotating teams of scientists. On the other side, the scientists and graduate students that remained at the National Microbiology Laboratory redirected their research efforts to studying this new strain of Ebola virus. Indeed, initial sequencing analysis of the virus revealed that it was substantially different from previous outbreak strains and raised some questions as to whether these differences were responsible for phenotypic differences observed in West Africa, such as higher virulence or transmission of the virus. It is through the CIHR Innovative Ebola Operating Grant that we sought to answer these questions.

The commencement of the funding period coincided with the completion of an ongoing experiment in non-human primates that was aimed at characterizing the course of disease for the new West African Ebola virus strain. This led to a peer-reviewed publication that showed that one of the new variants isolated at the very beginning of the outbreak was capable of replicating to higher levels and caused more tissue damage than a strain from a previous outbreakFootnote 1. With CIHR's support, the next step was to evaluate whether these findings correlated with enhanced transmission of the virus, a critical question highly relevant to the extended spread of Ebola virus in West Africa. Also, studies aiming at the identification of the molecular determinants of pathogenicity, a critical aspect of our understanding of how the virus causes damages leading to death, were initiated with collaborators in the UK. The ground-breaking findings associated to this work were published late in 2016Footnote 2.

In parallel, transmission was assessed in different systems. First, we sought to develop a new animal model for transmission of Ebola virus that would allow us to answer many hypotheses. This new model was developed in ferrets after our group established high susceptibility of this animal species to Ebola virusFootnote 3. The manuscript for the newly developed transmission model in ferrets is currently in preparation for submission to a peer-reviewed journalFootnote 4. Transmission was finally systematically evaluated in non-human primates, an animal species where transmission of Ebola virus has never been consistently observed. Unexpectedly, transmission of Ebola virus was observed between NHPs (with or without direct contact) within the BSL-4 environment. This critical finding led to the study of Ebola virus replication in the airways of humans infected during the outbreak in West Africa. The presence of Ebola virus in the airway and signs of active replication were reported early in 2017Footnote 5.

Dr. Kobinger and his team has always made it a priority to be as transparent as possible with ongoing experiments and to present our findings whenever possible. In this spirit, Dr. Kobinger and one of his graduate students, Mr. de La Vega, were invited to present these findings at the International Filovirus Symposium in Belgium, in the form of both oral and poster presentations. This led to a subsequent invitation to Dr. Kobinger to present these results at the FANG (Filovirus Animal Non-Clinical Group) meeting in Maryland in April 2017. In addition, Dr. Kozak also presented these findings to a clinical audience at the city-wide infectious disease rounds at the University of Toronto, which has sparked the interest of the medical community. Dr. Kozak is beginning several new projects looking at the clinical and diagnostic implications of our findings. The scientific observations obtained from the transmission experiment in NHPs will be submitted for publication as soon as all the analyses are completed (expecting summer 2017)Footnote 6.

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