A newly published paper in scalpel Shows that an experimental vaccine against Marburg virus (MARV) was safe and induced an immune response in a small clinical trial for the first time in a human. The vaccine, developed by researchers at the National Institute of Allergy and Infectious Diseases (NIAID), is part of the National Institutes of Healthcould one day be an important tool for responding to the Marburg virus outbreak.
This first-of-its-kind human study tested the first phase of an experimental MARV vaccine, known as cAd3-Marburg, that was developed at NIAID’s Vaccine Research Center (VRC). This vaccine uses a modified chimpanzee adenovirus called cAd3, which is no longer able to replicate or infect cells, and displays a glycoprotein on the surface of MARV to trigger immune responses against the virus. The cAd3 vaccine platform has shown a good safety profile in previous clinical trials when used in the Ebola virus and Sudan virus validation vaccines developed by VRC.
Marv virus, a filovirus from the same family as the Ebola virus, causes a rapidly progressing febrile illness that leads to shock and death in a significant proportion of infected individuals. Many scientists believe that an outbreak of MARV in humans begins when the virus jumps out of its primary animal host, which is likely to be some chronically infected bats in sub-Saharan Africa. Symptoms of Marv’s disease are similar to those of Ebola virus disease and can include fever, headache, chills, rash, abdominal pain, vomiting, and diarrhea. As the disease progresses, patients may experience multiple organ dysfunction, delirium, and significant bleeding from the gastrointestinal tract or other sites that may lead to death. There are no specific vaccines or treatments available for Marv’s disease, except for supportive care. While some experimental vaccines have been previously tested, none have been shown to be highly effective and provide lasting protection. In African regions where the Marburg vaccine is most needed, a single-dose vaccine that can protect recipients over a long period of time will be an important part in suppressing outbreaks.
In this study, 40 healthy adult volunteers were enrolled at the Walter Reed Army Institute Research and Clinical Trials Center in Silver Spring, Maryland. They received a single dose of a low-dose vaccine (1 x 1010 particle units) or a higher dose (1 x 1011 particle units). For safety, volunteers were enrolled in a dose-escalation plan. Three participants received a lower dose. Then, when they did not show severe adverse reactions after the first seven days, the experiment proceeded to enroll the remaining 17 volunteers. The same procedure was also used for the higher dose group. The volunteers were monitored for adverse reactions to the experimental vaccine and evaluated at regular intervals for 48 weeks to track their immune responses.
The trial’s safety results were encouraging: there were no serious adverse events, and the experimental vaccine was well tolerated. One participant in the high-dose group developed a fever after vaccination, but it was gone the next day. In addition, the experimental vaccine appears to induce strong and long-lasting immunity to the MARV glycoprotein: 95% of trial participants showed a strong antibody response after vaccination, and 70% maintained this response for more than 48 weeks.
Plans are in place for further trials of the cAd3-Marburg vaccine in Ghana, Kenya, Uganda and the United States. If additional data support the promising results seen in the Phase 1 trial, the cAd3-Marburg virus vaccine could one day be used in emergency response to MARV outbreaks.
