The second ever real-life test of an Ebola vaccine began today in Sierra Leone. It is unlikely, however, to achieve its main goal: proving that the vaccine, a livestock pathogen modified with an Ebola surface protein, protects humans against the deadly disease. That’s because there simply may not be enough patients.
Since peaking at the end of November, the number of newly reported cases in Sierra Leone has dropped steadily, from 95 4 weeks ago to just 21 last week. That makes it very unlikely, that the trial—led by the U.S. Centers for Disease Control and Prevention (CDC) and the Sierra Leone Ministry of Health and Sanitation—can get a statistically significant result, says Stephan Becker, a virologist at the University of Marburg, Germany.
Together with the College of Medicine and Allied Health Science at the University of Sierra Leone, CDC and the ministry aim to vaccinate 6000 nurses, doctors, and other frontline workers battling the Ebola outbreak over the coming months. The vaccine—developed by the Public Health Agency of Canada’s National Microbiology Laboratory and now backed by pharmaceutical giant Merck—was made by stitching a gene coding for an Ebola surface protein into the vesicular stomatitis virus (VSV), a relative of rabies that infects cattle, horses, and pigs.
There has been no discussion of scrapping the trial, which may end up costing about $25 million, said Anne Schuchat, director of CDC's National Center for Immunization and Respiratory Diseases at a press conference today. “However, we did decide that it was very important to adjust our design to maximize the chance that we would be able to answer key questions,” she said. Instead of a classic stepped-wedge trial, which introduces a vaccine to different groups in phases and then compares results from those who were vaccinated early with those who were vaccinated later, the investigators are now starting a randomized trial, in which individual participants will receive the vaccine either immediately or after a period of 6 months. The new design increases the time that unvaccinated people—the control group—will be observed.
At the end of the study, researchers will compare the rates of infection among the vaccinated and unvaccinated groups. Statistical modelling suggests that to get a significant result, 67 participants would have to be infected with Ebola if the vaccine is 50% efficacious. If the vaccine is 90% efficacious, as few as 17 infections might yield a significant result.
Even with a low probability of getting those results, Becker says going ahead with the trial—called STRIVE (Sierra Leone Trial to Introduce a Vaccine against Ebola)—is a good idea because it may yield important information about the VSV vector. That could be helpful in designing other vaccines based on that virus. “And the trials might still save a few lives while doing that,” he says. The researchers are also collecting data on how safe the vaccine is and how well it stimulates the immune system, information that might pave a way for the vaccine to be licensed even if there is no final proof of its protection. An ongoing trial may also prove crucial if there is another uptick in cases, says John-Arne Røttingen of the Norwegian Institute of Public Health in Oslo.
STRIVE is the second phase III trial of this particular Ebola vaccine candidate. Last month, a World Health Organization (WHO)–sponsored trial was launched in Guinea. In that trial, called a ring vaccination, rings of people living close to newly discovered Ebola patients are identified and vaccinated either immediately or after 21 days. So far, five of a planned 190 rings have been vaccinated. There have been more new Ebola infections in Guinea than in Sierra Leone over the last several weeks, making the WHO trial more likely to yield results.
*The Ebola Files: Science and Science Translational Medicine have made a collection of research and news articles on the Ebola virus and the current outbreak freely available to researchers and the general public.