EBOKON: Strengthening Ebola Research
Focussing on Ebola virus
The German Center for Infection Research (DZIF) has initiated a consortium to strengthen Ebola research and close the knowledge gaps as quickly as possible in the fight against the epidemic. This network, “EBOKON”, will be supported by the Federal Ministry of Education and Research (BMBF) with 2.3 million Euros until the end of 2015.
“The current Ebola outbreak in West Africa has shown that there are still many open research questions about this virus. They need to be answered as quickly as possible in order to end the epidemic and be better prepared for the long-term,” explains Professor Stephan Becker, EBOKON coordinator from the University of Marburg. The virologist also heads the DZIF Thematic Translational Unit “Emerging Infections” which works with closely related themes. The ten projects now being supported are integrated into international Ebola activities, including those of the WHO, among others. They address the most urgent questions: How can safe vaccines be developed and implemented quickly? How can the virus be contained? Which animal models can help answer questions in the fight against Ebola? How can the virus and its spread be monitored better, in present and in future?
The ten EBOKON projects will be conducted over the next 14 months. Existing DZIF structures and facilities, as well as the expertise brought in by the participating scientists in the field of Ebola research, will make possible a fast implementation of measures to fight the Ebola epidemic in West Africa. These projects will be supported in addition to other ongoing DZIF projects working on Ebola. This broadly based collaboration project will be brought together and strategically aligned under the roof of the DZIF.
Projects and contact persons
Developing MVA vector vaccines to prevent Ebola virus infections
The aim of this project is the preclinical development and characterisation new vaccines against Ebola virus infections, based on recombinant vaccinia viruses MVA. There are currently two promising candidate vaccines against the Ebola virus available, which are yet to be tested in humans. Clinical trial preparations are underway and an implementation is expected at the beginning of 2015. These vaccines are either effective against two subtypes of the Ebola virus (adenovirus-based vaccine), or monovalently effective against the Zaire Ebola virus only (VSV-based vaccine). However, there are currently three independent virus outbreaks in Africa, highlighting the need for multivalent Ebola vaccines. The project will contribute to developing broad and specific Ebola virus vaccines which can quickly be drawn upon for testing in clinical settings.
Developing and validating pan-Ebola vaccination strategies
The antibody cocktail (ZMAPP) seems to cause significant improvement in some people with Ebola infections. However, the cocktail is globally no longer available and the production of a few new doses takes months. There is currently a lack of concepts for rapidly developing and producing passive immune therapies. This project compares different vaccination strategies and validates the most promising ones with further experiments in Marburg.
Analysing and inhibiting Ebola virus entry into host cells
There are currently no antiviral drugs available against Ebola viruses. One potential mechanism of anti-Ebola virus therapy could be to inhibit its entry into target cells. Ebola viruses contain glycoprotein GP, a substance which mediates their entry into host cells. In order to identify potentially highly effective antiviral drugs, this project will investigate the interaction between the virus and host cells and how it can be inhibited.
Developing fluorescing recombinant Ebola viruses (Guinea strain) to enable rapid testing of emerging mutations in the virus genome and their pathogenic implications; Testing vaccine effectiveness and antibody therapies under BSL-4 conditions
In the Ebola virus outbreak in West Africa, several mutations in the Ebola virus genome which occurred during human-to-human transmission have been discovered. The significance of these mutations for the biology of the virus and its pathogenic effects is currently totally unclear. This project aims to characterise emerging mutations. For this, recombinant Ebola viruses are constructed to additionally carry information for a fluorescent marker in their genetic information. These viruses can then be tracked in living infected animals, through which the effects of a mutation on the course of disease can be investigated.
Using chimeric mouse models to investigate Ebola virus immunity and pathogenesis
Immune responses to Ebola viruses are not well understood because insufficient numbers of patient samples have been available up to now. For example, it is not known how the T cell response of patients who survive Ebola infections differs to immune responses in cases where infection was fatal. Mouse models in which the virus can replicate will be used to help investigate these questions. This project is in collaboration with the Heinrich Pette Institute in Hamburg.
Systems vaccinology: Hereditary predictors of Ebola virus induced adaptive immunity
There is very little data available about immune responses to Ebola virus vaccines. A clinical phase I trial with an Ebola virus vaccine (VSV-EBOV) in Hamburg has already been planned, which will also allow for more insight into the immune responses. It is expected that investigations into the initial post-immunisation stage, in which the innate immune system triggers the acquired immune response, will deliver valuable information regarding vaccination success.
Conducting a phase I Ebola vaccination trial
The VSV-based Ebola vaccine is a promising candidate vaccine, being clinically tested at four locations coordinated by the WHO. A trial led by Marylyn Addo is due to be conducted at the UKE in Hamburg. Besides this, the Albert-Schweitzer Hospital in Gabon will also be conducting a phase I trial sponsored by the University of Tübingen. The urgently needed staff for this will be financed by EBOKON.
Investigating the filovirus transmission chain in an industrialised West African country.
Fruit bats are known to be the natural reservoir of Ebola virus. However, the exact route of transmission to humans is unknown, as is the question of whether other infected animals play a role in the spread of the epidemic. Being able to prevent epidemics like this in future will depend on having answers to these questions. In this project, researchers will investigate the entire possible transmission chain of Ebola viruses and other so-called filoviruses with existing patient samples in Ghana - a relatively well-industrialised West African country - without having to do elaborate field work.
Minimising the risk of further Ebola virus spread
9a: Investigating a possible secondary reservoir in animals in West Africa: Due to the wide spread of the Ebola, animals may potentially become a secondary reservoir for the virus. In this project, animals in the outbreak areas will be tested for Ebola viruses as well as for Ebola antibodies, in order to identify possible secondary reservoirs and the consequent risks. The results could be used to implement appropriate measures against this.
9b: Developing adaptive, interactive software to assess absolute risk of Ebola imports in global air traffic network hubs: Individual cases of Ebola infections may be transported into further countries through international air traffic. Besides being dependent on air traffic movements, the risk of transporting the virus also depends on many other factors (e.g. the number of cases in West Africa) which have so far not been sufficiently taken into consideration in the respective mathematical models. In this project, an existing model for risk assessment will be developed further.
9c: Developing, implementing and evaluating a follow-up tool for staff in Ebola treatment centres and returning travellers from Ebola epidemic regions: Health monitoring for helpers and other persons who return from missions in regions with Ebola is to be made simpler by means of mobile data entry, an optional follow-up network is to be developed.
Ebola surveillance with mobile real-time data transmission in Nigeria
In past Ebola outbreaks, monitoring people who had had contact with people suffering from Ebola infections was an essential tool for containing the epidemic. However, the current outbreak has taken on a scale where such measures can only be implemented by means of very modern technology, especially under West African conditions. A new system using centrally connected mobile telephones as a steering instrument is being developed in Germany, together with Nigerian partners and will be piloted in Nigeria shortly.
