Results from PREVAIL I--a large Ebola vaccine study that enrolled more than a thousand Liberians at Redemption Hospital in Monrovia during the first few months of 2015-- have been published in the October 12th issue of The New England Journal of Medicine.
The results show that the two test vaccines, cAd3-EBOZ and rVSV-ZEBOV, pose no major safety concerns and can produce immune responses within one month after vaccination that last for at least one year.
The study was the first to be conducted by the Partnership for Research on Ebola Virus in Liberia, or PREVAIL. PREVAIL operates under the umbrella of a Joint Liberia-U.S. Clinical Research Partnership established in 2014 to assist Liberia develop vaccines and therapeutics to tackle Ebola.
From February 2 through April 30, 2015, PREVAIL enrolled 1,500 men and women ages 18 and older in the study. Enrollees had no reported history of Ebola virus disease. The participants were divided at random into three groups of 500 each. One group received one test vaccine, the second group the other test vaccine, and the third group received a placebo (saltwater injection). It was important to include the placebo so that the research team could, compare how well the test vaccines worked.
Participants gave blood samples before vaccination and again at one week, one month, six months, and one year post-vaccination. The study team tested each of these samples for infection-fighting antibodies against the Ebola virus.
After one week, only modest levels of antibodies were seen with both vaccines. However, by one month, 71 percent of cAd3-EBOZ recipients and 84 percent of rVSV-ZEBOV recipients developed an antibody response compared with three percent of placebo recipients.
At one year, the antibody responses were largely maintained in both groups: 64 percent of cAd3-EBOZ recipients and 80 percent of rVSV-ZEBOV recipients had antibody response compared with seven percent of placebo recipients.
Some participants who received the test vaccines had temporary mild to moderate side effects, including headaches, muscle pain, fever and fatigue. Overall, no major safety concerns related to the vaccines were identified.
"We were extremely thankful to have enrolled more than a thousand Liberian volunteers into the trial so quickly and to have more than 98 percent of those who enrolled return for their follow-up visits during the year," says Dr. Stephen B. Kennedy, senior research scientist at the UL-PIRE Africa Center, an infectious disease research center based at the University of Liberia, and Co-Principal Investigator of the study.
"The study was a true collaboration with the people of Liberia who participated and made it a success. To each and every one of them, we extend our deep gratitude."
PREVAIL conducts collaborative biomedical research in accordance with best practices, to advance science, strengthen health policy and practice, and improve the health of Liberians and people worldwide.
"We cannot succeed in the fight against Ebola unless we identify primary prevention tools. Through PREVAIL, we are developing vaccines and therapeutics in our region that can help Liberians and the rest of the world, "said Tolbert Nyenswah, Director General of the National Public Health Institute of Liberia (NPHIL) and Chairman of the Executive Committee of PREVAIL.
The PREVAIL I study will continue to follow for several years those who had enrolled into the study to determine the long term benefits of the vaccines.
The co-leaders of the study are Dr. Kennedy; Fatorma Bolay, PhD, Director, Division of Biomedical and Public Health Research at NPHIL; and Dr. H. Clifford Lane, Deputy Director for Clinical Research and Special Projects at the National Institute of Allergy and Infectious Diseases (NIAID), part of the US National Institutes of Health (NIH), which sponsored the study in collaboration with the Liberian Ministry of Health (MoH).
"By developing research capacity and infrastructure to answer questions about Ebola and other infectious disease that are threats to global health, PREVAIL has become a successful model for the implementation of clinical trials during health outbreaks in resource-constrained environments," noted Dr. Kennedy.
The cAd3-EBOZ vaccine candidate was co-developed by NIAID's Vaccine Research Center and GlaxoSmithKline (GSK), while rVSV-ZEBOV, initially engineered by scientists from the Public Health Agency of Canada, is now licensed to Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., (Merck). GSK and Merck provided the test vaccines for the study.