PREVAIL (Partnership for Research on Vaccines and Infectious Diseases in Liberia) was established in 2014 to conduct clinical research on Ebola therapeutics and vaccines. Governed by multiple, global organizations, the PREVAIL network has since expanded its research to other locally important diseases, including HIV, malaria and COVID-19. However, Ebola virus disease (EVD) remains a priority, and PREVAIL, with its partners in the Partnership for Research on Ebola VACcinations (PREVAC), recently published the results from clinical trials of three vaccine regimens against Zaire EVD in the New England Journal of Medicine. The publication’s authors included PREVAIL team members Mark Kieh, MD, MSMHC, and Stephen B. Kennedy, MD.
EVD outbreaks continue to occur.
Since the Ebola virus was first discovered in 1976, outbreaks have occurred in multiple countries, with an average EVD case fatality rate of ~50% (ranging from 25% to 90%).
With the high morbidity and mortality as well as the negative financial and public health consequences caused by EVD, finding effective, safe vaccines is of the utmost priority in affected countries. Of the species in the Ebolavirus genus, four can cause disease in humans: Zaire, Bundibugyo, Sudan and Taï Forest. Zaire ebolavirus is the cause of most of the recorded EVD outbreaks and is the deadliest, with case fatality rates of 70%-90%. The rVSVΔG-ZEBOV-GP (ERVEBO®) vaccine is approved to prevent Zaire EVD in people at least 18 years old, but there are currently no licensed vaccines against the other strains.
The largest and most complex EVD outbreak occurred due to Zaire ebolavirus in West Africa in 2014-2016; it resulted in more cases and deaths than in all other outbreaks combined and spread throughout countries including Guinea, Sierra Leone and Liberia. More recent outbreaks include a 2022-2023 outbreak of Sudan ebolavirus and a 2019 outbreak of Zaire ebolavirus in Uganda. Seven years after its first EVD outbreak, Guinea experienced another in 2021, caused by Zaire ebolavirus. The Democratic Republic of Congo experienced its eleventh EVD outbreak in 2020, a recurrence of the Zaire ebolavirus from the previous outbreak in 2018 and a new Zaire ebolavirus.
PREVAC’s randomized, placebo-controlled trials provide further evidence of the efficacy and safety of Ebola vaccines.
Since effective prevention of infection is critical to minimize the future impact of EVD, determining the characteristics of current and investigational vaccines is needed. To help address ongoing questions about the rapidity of immune responses and vaccine durability and safety for Zaire EVD, the PREVAC study team conducted two randomized, placebo-controlled trials of three vaccine regimens:
In these studies (one for adults and one for children), 1400 adults and 1401 children in Guinea, Liberia, Mali and Sierra Leone were randomized to the vaccination groups or placebo. The study team followed the groups for 12 months to determine the antibody response and document any safety concerns. Immune responses were observed at 14 days and continued through the full 12-month period. These immune responses were stronger than those in the placebo group.
The most common side effects were reactions at the injection site and symptoms such as feverishness or headache — all were mild to moderate and occurred primarily in the week after the injection.
The study results showed that all three vaccination strategies provided an immune response and were generally safe in both adults and children. Because of the different platforms and mechanisms of each vaccine, the study team was not able to compare the amount of protection provided by each strategy. In addition, because no one in the study was exposed to EVD, the team was unable to assess whether the immune response protected against infection. These are areas that should be explored in future studies, and the PREVAC team is currently investigating whether a later booster affects the outcomes.
FHI Clinical is proud to contribute to research for vaccines against EVD.
The FHI Clinical team previously contributed to a clinical trial of vaccination during the 2014-2016 outbreak and is excited, as part of PREVAIL, to have been part of this latest important work to find efficacious and safe vaccines against EVD.
In addition to Dr. Kieh and Dr. Kennedy, the following PREVAIL team members contributed to the trials: Benetta C. Andrews, Moses Badio, Luke Bawo, Teedoh Beyslow, Fatorma Bolay, Sarah Browne, Michael Chea, Joseph Boye Cooper, Lawrence Fakoli, Mosoka Fallah, John Fayiah, Kokulo Franklin, Maima Gray, Madison Joe, Melvin Johnson, Hassan Kiawu, David Kollie, Catherine Kpayieli-Freeman, Shadrach Langba, Mameni Linga, Julia Lysander, Marvington Mambiah, Moses B.F. Massaquoi, Philip Sahr, Bode Shobayo, Sienneh Tamba, Julius Teahton, Jemee Tegli, Elvis Towalid, Tijili Tyee, Cecelia Wesseh, Barthalomew Wilson and Quiawiah Yarmie.
PREVAIL was founded as a collaboration between local and international organizations, including the U.S. National Institutes of Health (NIH), the World Health Organization (WHO) and FHI Clinical. Since its inception, PREVAIL has developed clinical research infrastructure across four sites in Liberia: John F. Kennedy Medical Center (JFKMC), Redemption Hospital, CH. Rennie Hospital and Duport Road Clinic. Resources also include a research lab at Liberia Institute for Biomedical Research (LIBR) and an imaging suite at JFKMC.
In September of 2020, we expanded our role to full operational management. We provide experienced oversight, oversee and facilitate the execution and contractual requirements of all in-country logistics, and help sustain the ability of the network’s research-ready sites to conduct high-quality studies in collaboration with sponsors and research teams.