The initial results of a clinical Phase I trial of a potential vaccine against the dreaded Ebola virus are now available at the Hamburg-Eppendorf University Medical Center (UKE). As this trial was being conducted, scientists in Geneva (Switzerland), Lambaréne (Gabon), and Kilifi (Kenya) were also testing the “rVSV-ZEBOV” vaccine on a total of 158 healthy adult volunteers. The initial results were published today in the New England Journal of Medicine (NEJM).
“We are delighted that the UKE supports the global fight against Ebola in this way, together with other scientists and experts from the German Center for Infection Research (DZIF). A vaccine is still urgently needed, since the current Ebola epidemic has not yet been defeated and the possibility of future outbreaks cannot be ruled out,” said Prof. Dr. Burkhard Göke, Medical Director and Chief Executive Officer of the UKE.
“We have been successful in initiating this important vaccine trial so quickly and carrying it out successfully together with the other centers despite significant regulatory, logistical, and organizational hurdles,” says Prof. Dr. Ansgar W. Lohse, Director of the First Department of Internal Medicine. “Never has a vaccine been developed as quickly as in the case of Ebola.”
Phase I of the clinical trial for the vaccine candidate termed “rVSV-ZEBOV” has been ongoing in the Clinical Trial Center North (CTC North) at the UKE since November 2014. “The preliminary results for tolerability, safety, and the immune response to the vaccine candidate are promising,” explains Prof. Dr. Marylyn Addo.
“The adverse reactions were generally mild or moderate and within the limits of what can be expected when using live vaccines.” The specialist for infectious diseases headed the trial at the UKE in Hamburg and is one of the authors of the recent publication outlining the results for all four sites. The scientists involved are participants in VEBCON, a consortium of experts founded by the WHO, the goal of which is rapid and coordinated clinical testing of the Ebola vaccine in Africa.
About the trial
A total of 158 healthy volunteers at the four locations were vaccinated with increasing doses of the potential vaccine. A double-blind study was conducted in Geneva. The rVSV-ZEBOV vaccine used is an attenuated, genetically modified strain of vesicular stomatitis virus (VSV), which bears a surface protein of the Ebola virus. The goal is to help the vaccinated person's immune system produce antibodies to prevent an outbreak of the disease upon contact with the Ebola virus. For the first time, scientists have tested the vaccine's safety and tolerability in people, as well as the human immune response to it.
In the Clinical Trial Center North at the UKE, volunteer subjects received the potential vaccine. They then remained under observation in the hospital for three to five days, after which they were closely monitored as outpatients. Prof. Addo: “The commitment of the subjects was immense; many volunteered well before the start of the trial. This greatly facilitated our work and contributed to the trial's success.”
Safety and tolerability: No serious adverse reactions associated with the vaccine have been observed. Since it is a live vaccine, small amounts of the vaccine virus were found in the blood, as expected, but only in the first few days. Virus replication appears to be controlled and limited by the immune system. No viruses were detected in saliva and urine.
Effect on the immune system: The vaccine stimulated the immune system of all participants to produce antibodies specifically targeting the Ebola surface protein. The antibodies were able to inhibit infection by the Ebola virus in vitro. “These results show that the new vaccine has the potential to be used even during dramatic outbreaks such as the current Ebola virus outbreak,” says Prof. Dr. Stephan Becker, whose laboratory at the Philipp University of Marburg evaluated the immune responses of all trial participants.
The initial results will now be utilized in further trials in West Africa that will use the optimal doses previously determined. In Guinea, where the Ebola epidemic still claims many lives, the vaccine is already being tested in a larger Phase II/III trial based on the initial results of the vaccine trial described and people in contact with Ebola patients are being vaccinated. About 10,000 people are expected to participate in these trials in the coming weeks.
The German Center for Infection Research (DZIF) supported the preparation of the trial at the UKE in Hamburg. DZIF, the Federal Ministry of Health (BMG), and the British Wellcome Trust provided the funding to prepare and implement the clinical trial. The Canadian Health Authority donated the vaccine candidate to the WHO, which then made it available for these trials. All parties involved are thus responding quickly and jointly to the dramatic Ebola epidemic in West Africa. In preparing the trial, the DZIF scientists in Hamburg, Gießen-Marburg-Langen, and Tübingen worked closely with the Paul Ehrlich Institute (PEI), which, as a partner of the DZIF, supports research into new vaccine platforms. In Hamburg, the trial was conducted in close collaboration with the Heinrich Pette Institute and the Bernhard Nocht Institute.
Commitment of the UKE to the fight against Ebola
In August 2014, a WHO employee infected with the Ebola virus was admitted to the UKE. After five weeks in special isolation, he was discharged as cured in early October 2014. The attending physicians and infectious disease specialists at the UKE, the Bernhard Nocht Institute for Tropical Medicine (BNITM), and the German Center for Infection Research (DZIF) reported that the patient had to contend with serious complications. In addition to severe dehydration as a result of the Ebola infection, bacterial sepsis required further intensive care measures.
Selidji T. Agnandji, M.D.; Angela Huttner, M.D.; Madeleine E. Zinser M.D.; Patricia Njuguna M. M.D. et al. Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe — Preliminary Report. N Engl J Med, online first release on April 1, 2015. DOI: 10.1056/NEJMoa1411627
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