Ebola Vaccine Appears Effective, WRAIR Publishes Findings in NEJM
As the U.S. Department of Defense's largest biomedical research facility, the Walter Reed Army Institute of Research has once again demonstrated the U.S. military's expertise in responding to outbreaks of infectious diseases with its successful completion of a phase 1 clinical trial for an Ebola vaccine candidate, the recombinant vesicular stomatitis virus for the Zaire strain of Ebola.
Together with researchers from the National Institute of Allergy and Infectious Diseases, who completed their own phase 1 clinical trial, researchers at the WRAIR and NIAID published their findings from the trials in the New England Journal of Medicine April 1.
The trials, conducted independently but collaboratively, explored the safety and immunogenicity of the investigational vaccine when administered at different dosages.
The Public Health Agency of Canada developed the rVSV-ZEBOV and licensed the candidate to NewLink Genetics Corporation who, in turn, sublicensed to Merck Sharp & Dohme Corporation. The vaccine's intent for both pre- and post-exposure prophylaxis would allow both those exposed and those not yet exposed to Ebola to avoid developing Ebola virus disease.
When the 2014 Ebola epidemic occurred, it became clear to the U.S. government and the global community that they needed to quickly advance the development of a vaccine.
In response to this need, the Defense Threat Reduction Agency requested support from the WRAIR to prepare and execute a human clinical trial and develop a lab test to support the assessment of the vaccine's safety.
"When DTRA approached us, we redirected our personnel, mission and resources to meet the global need," said Col. Stephen Thomas, deputy commander of the WRAIR and senior author of the NEJM publication. "The WRAIR lab enterprise, which is both domestic and international, may look like a number of individual programs, but really we are a collection of science and science support professionals with expertise in infectious diseases. We have a number of platforms, capabilities and competencies that are generally applicable to whatever the DOD determines to be a threat."
With its adaptable platforms and capabilities, the military can direct and redirect its resources as the needs and requirements arise.
Past efforts include supporting vaccines licensed against Hepatitis A, Adenovirus Types 4 and 7 and Japanese encephalitis, not to mention major accomplishments like the HIV vaccine efficacy trial in Thailand and participation in Sanofi Pasteur's Dengue vaccine phase 3 trial in Asia. Notably, the WRAIR investigated every current malaria drug in the world and supported their clinical use, including the RTS,S that first demonstrated efficacy through studies at the WRAIR.
"Ebola was just the next thing in line. It's an exemplar of what we do on a day-to-day basis and what we have been doing since 1893," said Lt. Col. Jason Regules, deputy director of the Translational Medicine Branch within the WRAIR and co-lead author of the NEJM publication.
The WRAIR worked with NewLink, Merck and the DTRA to prepare for the clinical trial, execute the trial and analyze the data.
Preparation included working to meet the regulatory requirements, establishing logistical processes, helping design the study and the scientific activities that would characterize the vaccine's performance, writing the protocol and submitting the plans for an independent ethical review.
Researchers had no difficulty in recruiting the 52 volunteers they enrolled.
"I think the scale of the human crisis that was occurring in Africa was such that really motivated people to step forward," said Regules. "This one caught everyone by surprise through its magnitude."
Combining both centers, 40 volunteers received a single dose of the vaccine candidate and 12 received a placebo. Researchers periodically assessed the volunteers for safety and collected blood samples to determine who developed antibodies.
Thirty-seven of 40 volunteers 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, with no significant side effects.
The vaccine intends to make the recipient's immune system react as if it has been exposed to the Ebola virus. If the vaccine recipient were ever naturally exposed to Ebola, the immune system would respond and protect the individual from developing the Ebola virus disease.
Scientists developed the vaccine by replacing a small portion of the VSV virus with a small, but important, component of the Ebola virus. By doing this, they can stimulate the desired anti-Ebola immune response without actually exposing the recipient to any risk of developing Ebola.
"It tricks the body's immune system into thinking you've been exposed to Ebola and prepares a protective response in the event you ever are actually exposed to the virus," said Thomas.
Researchers assessed the antibody response using two different methods, a quantitative assay that examined the total amount of antibodies in the subject, and a qualitative assay that evaluated the antibodies' function.
"We saw a robust immune response following a single dose of the vaccine, which could be particularly useful in outbreak interventions," said Thomas.
The study's mission was to produce results that would help determine the design of the studies in West Africa, for which the rVSV-ZEBOV is one of two Ebola vaccines being tested.
"These pivotal early studies helped inform dose selection for testing of rVSV-ZEBOV vaccine in a large-scale clinical trial in West Africa," said Regules. "We were gratified to see that the vaccine was not associated with significant adverse effects in this very carefully monitored study."