The results of a recent Phase IB study show that the novel Ebola vaccine, V920, was well-tolerated and “stimulated a rapid onset of binding and neutralizing antibodies,” which persisted for up to 1 year.
The 2014 Ebola virus outbreak in western Africa—and the media-fueled global panic that ensued—highlighted the need for a viable vaccine against the disease.
Now, research suggests such a vaccine may be in the pipeline; arguably welcome news in light of the recent 2017 Ebola outbreak in the Democratic Republic of Congo.
In a Phase 1B study published June 9, 2017 in the journal Lancet Infectious Diseases, researchers found that the novel vaccine, called rVSVΔG-ZEBOV-GP or V920 for now, was well-tolerated and “stimulated a rapid onset of binding and neutralizing antibodies,” which persisted for up to 1 year, when administered at a dose of 2 × 10⁷ PFU dose. V920 is a live attenuated recombinant vaccine in which the vesicular stomatitis virus envelope glycoprotein is replaced by the envelope glycoprotein of the Kikwit strain of the Zaire Ebola virus. It was originally developed in the National Microbiology Laboratory of the Public Health Authority of Canada.
“[These] results… strengthen the interim estimates and conclusions made earlier that the V920 vaccine has high protective efficacy and eﬀectiveness to prevent Ebola virus disease,” study coauthor Beth-Ann Coller, PhD, Vaccine Development Team Leader at Merck, told Contagion®. “We believe that safe and effective Ebola vaccines will be critical to a comprehensive Ebola prevention and control program as well as to containing future outbreaks.”
For the Phase IB study, the authors enrolled and randomly assigned 513 healthy adults to 1 of 2 cohorts at 8 US-based study sites to receive a single IM injection of V920 or placebo, at 1 of 4 doses (3 × 10³ PFU, 3 × 10⁴ PFU, 3 × 10⁵ PFU, or 3 × 10⁶ PFU in cohort 1 and 3 × 10⁶ PFU, 9 × 10⁶ PFU, 2 × 10⁷ PFU, or 1 × 10⁸ PFU in cohort 2). In cohort 1, 256 participants received the vaccine and 74 received placebo, while in cohort 2, 162 participants received the vaccine and 20 received placebo (1 participant did not receive the vaccine or placebo due to unsuccessful phlebotomy).
At the recommended 2 × 10⁷ PFU dose, the most common local adverse events within the first 14 days following vaccination were arm pain and injection-site tenderness. The most common systemic adverse events were headache, fatigue, myalgia, subjective fever, shivering or chills, sweats, joint aches and pain, objective fever, and joint tenderness or swelling. Postvaccination arthritis and dermatitis, both common adverse events cited in earlier trials, occurred in 4.5% and 5.7%, respectively, of those who received V920, versus 3.2% and 3.2%, respectively, of controls.
Notably, in terms of possible vaccine efficacy, antibody responses were observed in most of the study participants by day 14 following administration. Among those who received the 2 × 10⁷ PFU dose, the geometric mean IgG ELISA endpoint titer was 1624, seroconversion was 95.7%, the geometric mean neutralizing antibody titer (via PRNT360) was 250, and seroconversion was, again, 95.7%, with all responses sustained for 1 year.
Some Phase II and III studies of V920 have already been conducted, with results expected soon, and additional trials are underway, including the PREVAC trial under the auspices of the French National Institute of Health and Medical Research, the US National Institute of Allergy and Infectious Diseases, and the London School of Hygiene and Tropical Medicine.
“Our plans call for us to file for licensure as soon as possible,” Dr. Coller said. “In the meantime, we remain poised to distribute vaccine in the context of expanded access clinical trials in response to an Ebola outbreak should an emergency request be made.”
In a commentary published with the study findings, Elizabeth C. Clarke and Steven B. Bradfute of the Center for Global Health at the University of New Mexico, write that, “The strength of this study lies in its demonstration of the longevity of neutralizing antibody responses after vaccination… Good longevity of immune responses is particularly positive for future development of Ebola virus vaccines, since it could increase the utility of the vaccine for health-care workers and people in endemic regions who are most likely to be exposed to the virus over a prolonged period.”
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.