The need for a vaccine for the Ebola virus that provides “durable immune response” is known to be key for protecting at-risk populations and health care and aid workers in at-risk areas both during outbreaks as well as outside any known outbreaks.
Now, researchers from the University of Oxford in the United Kingdom, in partnership with Janssen Pharmaceuticals, believe they have demonstrated that an approach that includes heterologous primary and booster vaccination with adenovirus type 26 vector vaccine encoding Ebola virus glycoprotein (Ad26.ZEBOV) and modified vaccinia virus Ankara vector vaccine, encoding glycoproteins from Ebola, Sudan, Marburg, and Tai Forest viruses nucleoprotein (MVA-BN-Filo) fosters immunity for up to 1 year. The team published their findings in a research letter
printed in the March 14, 2017 issue of the Journal of the American Medical Association
Both the Ad26.ZEBOV and the booster MVA-BN-Filo vaccines were among the vaccine strategies evaluated by the World Health Organization (WHO) following the 2014-2015 West African outbreak of Ebola that generated headlines—and panic
—worldwide. Ad26.ZEBOV is produced by Janssen, while MVA-BN-Filo has been developed by Bavarian Nordic.
In what is believed to be “the longest duration follow-up for any heterologous primary and booster Ebola vaccine schedule,” the Oxford authors performed a randomized, placebo-controlled, observer-blind, Phase I trial enrolling 87 healthy participants aged 18 to 50 in the United Kingdom. In the end, 72 study subjects were randomized to 4 groups, each with 18 participants (3 placebo and 15 active vaccine). Those randomized in the active vaccine groups received either Ad26.ZEBOV (5 × 1010 viral particles) or MVA-BN-Filo (1 × 108 median tissue culture infective dose) first, followed by boosting with the alternate vaccine 28 days or 56 days later. In addition, an open-label fifth group consisted of an additional 15 participants vaccinated with Ad26.ZEBOV followed by MVA-BN-Filo 14 days later.
Of the 75 active vaccine recipients, 64 remained in the study through follow-up at day 360 (11 participants withdrew), and all maintained Ebola virus–specific immunoglobulin G responses throughout the study period. Indeed, 60% to 83% of the participants receiving Ad26.ZEBOV and MVA-BN-Filo booster had persistent vaccine-induced T-cell response, compared to 69% to 100% of the participants who received the reverse regimen. Similarly, between 60% and 90% of respondents on the vaccine regimen demonstrated persistent Ebola-specific CD8+ T cell response at day 360. Notably, no serious adverse events were recorded in any of the vaccine groups.
“Although no correlate of protection has yet been established, Ebola virus glycoprotein-specific antibodies appear to play an important role in immunity,” the authors wrote. “A strategy of preemptive use of an AD26.ZEBOV followed by MVA-BN-Filo immunization schedule in at-risk populations… may offer advantages over reactive use of single-dose vaccine regimens.”
However, the authors also acknowledged that an important limitation of their study is that it enrolled European subjects.
“Immune responses may differ in a sub-Saharan African population; these vaccine candidates are being assessed in this region,” they note in their concluding remarks. “Additional research is also warranted to explore the persistence of immunity beyond 1 year following immunization and response to booster doses of vaccine.”
Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.
To stay informed on the latest in infectious disease news and developments, please sign up for our weekly newsletter.