Will Ebola evolve to set off a pandemic?
Ebola research for the future - improving international cooperation
How can the Ebola virus be inhibited? How can pathogens and their spread be better monitored now and in the future? How can safe vaccines be developed and deployed quickly? "These were the most urgent questions that should be answered within the framework of EBOKON", explains the EBOKON coordinator Professor Dr. Stephan Becker at the Philipps University of Marburg.
Vaccination is often the most effective protection against infection. A vaccination usually works by activating our immune system. Killed viruses or virus components simulate an infection in the body and thus stimulate the production of important defense cells and antibodies. This type of vaccination is also called active vaccination. Your advantage: It can protect you from the disease for a lifetime.
A newly developed Ebola vaccine, a so-called VSV vaccine, is already being clinically tested under the coordination of the World Health Organization (WHO) (see blue info box on page 13). The VSV vaccine works against a special strain of virus, the Zaire Ebola virus. Since there are several Ebola virus strains that can be involved in outbreaks, the EBOKON scientists are also working on developing a “platform” on which vaccines against different Ebola strains can be produced in a short time if necessary.
Professor Dr. Gerd Sutter, who works on this project at the Institute for Infection Medicine and Zoonoses at the Ludwig Maximilians University in Munich, explains: "These vaccines will have the advantage that they are more broadly effective and have a higher safety profile." on recombinant vaccinia viruses. These are viruses that cannot multiply in humans, but which nevertheless stimulate the production of the substances required for the immune system in the body, ”says Sutter. Theoretically, the information from several Ebola strains can be brought into these carrier viruses in order to produce a multivalent vaccine, i.e. a vaccine that is effective against several virus types. The experiments so far have shown that these vaccines trigger a good immune response.
Immune system and vaccination
For the development of effective vaccines and the further fight against Ebola, it is essential to better understand the immune response of the organism to a viral infection and the pathogenesis. In Hamburg, the course of the immune response to an Ebola infection could be scientifically investigated for the first time. "Up to now this was not possible for Ebola because we did not have a suitable investigation model to get clues for possible defense mechanisms," explains Dr. Cesar Munoz-Fontela from the Heinrich Pette Institute.
In an initial test on healthy people, a so-called clinical phase I study, researchers at the University Medical Center Hamburg-Eppendorf (UKE) are tracking how the innate immune system reacts to the immunization and triggers the vaccine effect. Initial data indicate that cytokines are produced as early as 24 hours after vaccination. Cytokines are important messenger substances in the immune system. In addition, within three days the body produces a large number of defense cells that belong to the innate immune system. These are monocytes, dendritic cells and natural killer cells, which provide non-specific immediate protection in the event of an infection. "We now want to find out to what extent this activation influences the later adaptive, i.e. acquired, response, which is crucial for a vaccination that is effective in the long term," explains Dr. Anne Rechtien from the UKE.
International cooperation for vaccine testing
In October 2014, the DZIF officially submitted the application for approval of a clinical phase I study for the vaccine candidate rVSV-ZEBOV. Exactly one month later, the first test participant will be vaccinated at the University Medical Center Hamburg-Eppendorf. The DZIF professor Dr. Marylyn Addo led the study in Hamburg. In parallel, tests were carried out at the DZIF partner institute in Lambaréné (Gabon) as well as in Geneva (Switzerland) and Kilifi (Kenya). "We were in contact almost every day with the WHO, which provided the vaccine and coordinated the preparation," explains Addo. The results were good: the vaccine had the potential to be used to protect against Ebola. Further studies in which many people are vaccinated have started very successfully in African countries. Further results can be expected in the coming year.
Antiviral drugs for Ebola
Preventing Ebola through vaccination is one of two goals. However, it is also important to develop antiviral drugs that can influence the course of the disease. For example, how could the virus be inhibited from entering the host cell? It is known that a certain protein, a glycoprotein of the Ebola virus, mediates the entry into human cells. Would that be a possible target for a drug? The Primate Center in Göttingen is investigating which cell factors are involved and how the viruses enter their central target in the body, the macrophages. Professor Dr. Stefan Pöhlmann from the Primate Center was able to identify factors that play an equally important role in various Ebola virus strains: both when the virus occurs and when it is inhibited. EBOKON also tests passive vaccination strategies such as antibody cocktails. One example of this is ZMAPP, an active ingredient that was used in the Ebola epidemic.
Track the spread of viruses
How can the spread of viruses be monitored and stopped in good time? This crucial question has triggered various research projects. One investigates the transmission chain of the Ebola virus. How is the virus transmitted from the fruit bat to humans, and do other animals perhaps also play a role in its spread? Professor Dr. Christian Drosten after. He heads the Institute for Virology at the University Hospital Bonn. Drosten examines existing samples from fruit bats and pigs, but also from humans. The samples come from Ghana, a relatively heavily industrialized West African country. The results of the study will provide information on how to better prevent a comparable epidemic in the future.
It will also be decisive whether the medical care and control of the sick and their contact persons works better in the event of a renewed outbreak. With the most recent epidemic, thousands of people had to be visited in often distant places in order to be able to care for them. As part of an EBOKON project, scientists from the Helmholtz Center for Infection Research (HZI) developed a novel IT system that is intended to help curb the spread of an infection in the future. The data of those affected can be quickly transmitted to a central register via centrally networked cell phones. A mobile phone app then enables symptoms and suspected cases as well as personal data to be easily recorded on site. The project was developed in cooperation with partners in Nigeria, at the Hasso Plattner Institute in Potsdam and with the software manufacturer SAP. “We already have indications that this system can work,” says Professor Dr. Gérard Krause from the HZI. The task now is to develop a viable market model.
There are still many unanswered questions about Ebola; However, through the interdisciplinary cooperation within the EBOKON network, knowledge was gained that will be helpful in the event of a new wave of infections. The DZIF will work intensively on further vaccines and strategies against Ebola as part of its focus on “Emerging Infectious Diseases”
German Center for Infection Research (DZIF)
In the German Center for Infection Research (DZIF) around 300 scientists from 35 institutions across Germany are jointly developing new approaches for the prevention, diagnosis and treatment of infectious diseases. The aim is so-called translation: the fast, effective implementation of research results in clinical practice. The DZIF is thus paving the way for the development of new vaccines, diagnostics and drugs against infections. The DZIF is funded by the BMBF and the federal states. You can find more information at www.dzif.de.
Professor Dr. Stephan Becker
Philipps University of Marburg
Karola Neubert and Janna Schmidt
Press and public relations
Office of the DZIF e. V.
0531 6181-1170 (or -1154)
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