An early-stage clinical trial of an experimental Ebola vaccine called VSV-EBOV found that the vaccine is safe and elicited a robust immune response, according to findings published today in the New England Journal of Medicine.
Two independent but coordinated Phase 1 studies, performed at the Walter Reed Army Institute of Research (WRAIR) and the National Institute of Allergy and Infectious Diseases (NIAID), explored the safety and immunogenicity of the investigational vaccine when administered at different dosages to 40 healthy adult volunteers.
“These pivotal early studies helped inform dose selection for testing of VSV-EBOV vaccine in a large-scale clinical trial in West Africa,” noted Lt. Col. Jason Regules at WRAIR, one of two co-lead authors of the paper. “We were gratified to see that the vaccine was not associated with significant adverse effects in this very carefully monitored study,” Regules added.
Scientists at the Public Health Agency of Canada’s National Microbiology Laboratory originally developed the VSV-EBOV vaccine candidate, one of two Ebola vaccines currently in large scale testing in West Africa. It has been licensed to NewLink Genetics Corp. in collaboration with Merck Sharp & Dohme Corp (Merck). The Ebola virus genetic material is delivered by a carrier virus (recombinant Vesicular Stomatitis Virus, or rVSV). The candidate vaccine does not contain Ebola virus and cannot cause Ebola virus disease.
The trials collectively enrolled 52 volunteers who received either the vaccine candidate or a placebo. Those volunteers given the vaccine received one of two different doses and volunteers were assessed on days 1, 3, 7, 14, and 28 to see if they developed anti-Ebola antibodies.
Twenty-six of 28 volunteers (93%) in the vaccine group showed the intended Ebola glycoprotein antibody response within two weeks of vaccination, and all of the volunteers had antibodies within 28 days of receiving the vaccine. Researchers saw a higher antibody response in the vaccine recipients who received the higher vaccine dose.
“We saw a robust immune response following a single dose of the vaccine, which could be particularly useful in outbreak interventions,” said Col. Stephen Thomas, WRAIR’s Deputy Commander and senior author on the paper. NIAID researchers are also looking at effects of an extra boost of the vaccine at day 28; results are expected later this year.
The volunteers tolerated the vaccine well. Thirty percent (12 out of 40) of those who received the vaccine experienced mild or moderate fever; in all but one case, fever appeared and resolved within 24 hours of vaccination. The VSV-ZEBOV vaccine is made from live, weakened VSV and self-limiting fever following immunization with a live virus vaccine is not unexpected.
Some volunteers in a separate, Swiss study of this candidate vaccine reported experiencing arthritis that started in the second week after vaccination. Therefore, volunteers in the NIH-WRAIR study were specifically queried about new arthritis symptoms. No episodes of frank arthritis were reported by any volunteer.
This clinical trial began in October during the peak of the devastating Ebola outbreak in West Africa. The combined experience of WRAIR and NIAID with Ebola, other infectious diseases research, and the conduct of human clinical trials enabled an agile shift in resources towards prioritizing the Ebola vaccine trial in just 11 weeks.
“The ongoing Ebola outbreak in West Africa is unprecedented in scope and duration,” said Anthony S. Fauci, M.D., director of NIAID. “The outbreak is slowly coming under control, thanks to extraordinary and multi-faceted efforts in the affected nations. However, there still are no licensed specific therapies or vaccines for Ebola. Until a safe and effective vaccine is available, the world will continue to be under-prepared for the next Ebola outbreak.”
All partners took part in developing the necessary assays to characterize vaccine safety and immune response. Critical support was provided by the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) and the DoD Chemical Biological Defense Program.
Read more at NEJM: A Recombinant Vesicular Stomatitis Virus Ebola Vaccine — Preliminary Report
