The New England Journal of Medicine, on Wednesday, published the results of the first placebo-controlled study of two vaccines against the Ebola virus, a research initiative funded by the US National Institutes of Allergy and Infectious Diseases (part of the National Institutes of Health) and Liberia’s Ministry of Health.
The safety and efficacy of vaccines to prevent Ebola virus disease (EVD) were unknown when the incidence of EVD was peaking in Liberia. A randomized, placebo-controlled phase 2 trial of two vaccines was rapidly initiated and completed in Liberia.
The study found that the two vaccines successfully created a powerful antibody response for 12 months, suggesting they both could be tools to save lives in a future epidemic of the deadly disease. By 1 month after vaccination, the vaccines had elicited immune responses that were largely maintained through 12 months.
A total of 1500 adults underwent randomization and were followed for 12 months. The median age of the participants was 30 years; 36.6% of the participants were women.
Five hundred participants received a vaccine developed by Merck & Co., 500 got one from GlaxoSmithKline PLC, which was based on work by the National Institutes of Health, and 500 received a placebo.
With the Merck vaccine, at one month, 83.7% of patients had developed antibodies to Ebola virus, versus 70.8% with the Glaxo vaccine and a negligible number, 2.8%, in the placebo group. The relationship of antibody responses was similar after 12 months, with 79.5%, 63.5% and 6.8% of patients, respectively, showing antibody response.
There is a “reasonable chance that either of these vaccines would play a role in preventing infection,” said H. Clifford Lane, deputy director for clinical research at the National Institute of Allergy and Infectious Diseases and a principal investigator in this study. NIAID is part of the National Institutes of Health. The Liberian Ministry of Health and other researchers also conducted the study.
In Dr. Lane’s view, given previously existing positive evidence from a Guinea study of the Merck vaccine, if doctors in a future epidemic had to choose, it would probably be the one from Merck.
That Merck vaccine was shown to be “highly efficacious” during the Ebola epidemic in Guinea by World Health Organization doctors writing in The Lancet in December. But the methodology of that study—including the lack of a placebo group—raised questions among some scientists about how conclusive those findings were.
Merck said the “safety and immunogenicity results observed” in this most recent research “are consistent with what we observed in other studies.” GSK said it is too early to know whether the immunity differences between the two vaccines “indicate a clinically meaningful difference.”
Ebola cases in Liberia began to dwindle early in 2015, and the outbreak there was declared over on May 9 of that year. By the time this work was fully under way, it was too late to see if vaccines actually prevented Ebola sickness and death.
It still was possible, however, to measure patients’ immune-systems’ response, measured by how many produced significant antibodies to the Ebola virus. Also, vaccine safety could be assessed, and both vaccines appeared safe.
NIH scientists now are evaluating antibody levels out to two years.
The level of serious adverse events was higher in the placebo group than either vaccine group, and “most of the serious adverse events were attributed to malaria,” the researchers wrote.