Evaluation of ebola vaccine safety and efficacy in a Prefecture of Guinea.

The Ebola outbreak in West Africa In 2015-2016, the largest ever recorded, included 28616 cases in Guinea, Liberia and Sierra Leone with 11310 deaths reported as of 10.6.2016, although but the course and outcome are unknown to many infected. At a meeting organized by the World Health Organization (WHO), in September 2014, it was recommended to accelerate clinical trials of promising vaccine candidates. A crucial need was to test the safety and efficacy of promising vaccines against Ebola virus, where vaccine doses were already available and these had been shown to provide protection in animals. A vaccine based on a modified virus (vesicular stomatitis virus (VSV)) capable of expressing Ebola surface proteins was selected on the advice of the WHO. To test the effect of the vaccine, the study was planned as a ring vaccination. This means that close contacts of patients with confirmed Ebola virus disease were vaccinated. The groups of contacts (rings) were randomized to immediate (intervention) or delayed (control) vaccination. The study was conducted in Guinea in the spring of 2015. In a sub-study, the immune response and safety of the Ebola vaccine were tested in health workers and support staff in Guinea. Blood samples were collected from 1,200 vaccinated individuals and 100 non-vaccinated controls to analyze the vaccine's ability to provide immune responses. We collaborated with laboratories in the UK, Germany, USA and Norway to analyze these samples to compare with other clinical studies with the VSV Ebola vaccine. The study was conducted in close collaboration with the local community and government and aimed to strengthen the capacity to carry out high-quality research in Guinea. The vaccination teams were from Guinea and have subsequently been engaged in other Ebola outbreaks in Africa. As part of capacity building, Guinea also requested training of methods for detecting meningitis in a laboratory in Conakry. In July 2015, the results of an interim analysis of the study were published in the journal The Lancet. The analysis showed that the VSV Ebola vaccine provided 100% protection against Ebola disease (95% confidence interval 74.7-100). The independent committee of international experts ("Data and Safety Monitoring Board") who reviewed the data recommended that the study continue but that the randomization should stop. The full study data from the study were published February 2017 in The Lancet, confirming previous data by demonstrating that the rVSV-ZEBOV vaccine provided significant protection against Ebola disease. No Ebola cases were detected among vaccinated individuals from day 10 after vaccination. Analyzes of blood samples from vaccinated individuals showed comparable responses as in trials with the vaccine in other countries. The WHO stated in the announcement of data that this study marked a turning point for outbreak health research and that this could be used as a basis for developing a global research framework for emerging diseases. Dr. Sakoba Keita, the national coordinator of the Guinea's Ebola response, stated that this was Guinea's gift to West Africa and the world, through their contribution to the study during the outbreak. The study was recognized by the journal Science as one of ten scientific breakthroughs in 2015, and on og National Geographic list of Top 20 scientific discoveries of decade i 2019. The ring vaccination method, which was demonstrated effectively in this study, has been adapted as a new tool to fight new Ebola outbreaks, and has been used to vaccinate over 250,000 individuals as of December 2019 in the Democratic Republic of Congo in connection with the second largest outbreak of all time. The vaccine was granted marketing approval in November 2019 in Europe and brings a new tool in mitigating outbreaks. Partners in the research study were: Norwegian Institute of Public Health, WHO, Republic of Guinea, University of Bern, University of Florida, London School of Hygiene and Tropical Medicine, Epicentre/MSF, Public Health England, Center for Vaccine Development, Mali and the European Mobile Lab (EMLab), Germany. Merck Sharp & Dohme provided the vaccine used in the trial. The study was funded by the WHO, UK Wellcome Trust, the UK Government through the Department of International Development, Médecins Sans Frontières, Norwegian Ministry of Foreign Affairs (through the Research Council of Norway's GLOBVAC programme and is part of the EDCTP2-Program supported by the European Union.), and the Canadian Government (through the Public Health Agency of Canada, Canadian Institutes of Health Research, International Development Research Centre and Department of Foreign Affairs, Trade and Development).

1.The research showed that a new Ebola vaccine was found effective in providing a high level of protection against disease. The Ring Vaccination Method, which was demonstrated effectively in this study has been used to vaccinate over 250,000 individuals in the DRC in 2019. The vaccine was licensed in November 2019, and this brings a new tool in mitigating outbreaks. 2.The innovative and field-tested study design will likely be a new and useful tool to test vaccines against diseases of similar transmission characteristics in the future. 3.The vaccine study marked a turning point for health research during outbreaks, and was key in developing the global research framework for emerging emergency preparedness called the WHO Blueprint for R&D, as well as the Coalition for Epidemic Preparedness Innovation. 4.The study led to significant knowledge transfer and accumulation of research competence among health workers and researchers in Guinea, exemplified by the use of Guinean teams in DRC.

The current outbreak of Ebola Virus Disease (EVD) in West Africa is by far the largest outbreak ever recorded: a total of 18,603 cases of EVD have been reported in three worst affected countries (Guinea, Liberia, Sierra Leone) by 17.12.2014, with 6915 reported deaths. A meeting held by the World Health Organization (WHO) in Sept. 2014 recommended expedited clinical trials with promising vaccine candidates, including phase 2/3 studies in EVD affected countries with front line workers or community members caring for patients with EVD in the community or at home. We therefore propose to evaluate EVD vaccines in Guinea in a way that would provide information on the vaccine efficacy and on the use of ring vaccination as a vaccine delivery and public health strategy. To be able to compare the risk of EVD in vaccinated and non-vaccinated, vaccination will be randomised to be immediate (intervention) or delayed (control) by 4-8 weeks. The study will be conducted in close engagement with the local community and authorities, and we aim to strengthen the capacity to conduct high quality research in Guinea. In addition, we intend to offer vaccine to frontline and healthcare workers (FLW/HCWs) in the study site area. This single-arm cohort study with, vaccination among FLW/HCWs, will be an opportunity to obtain data on safety. Blood will be collected for future immunogenicity studies of the vaccine as and when a correlate of protection is known, or to contribute to the scientific development of a correlate. The project group will decide on the most relevant vaccine candidate(s) to utilize when phase 1 trial results have been interpreted. Current vaccine candidates against EVD may reduce morbidity and mortality significantly, and the proposed research project has the potential to contribute to halting the present humanitarian crisis by means of a multidisciplinary and collaborative research effort.