VRC-MARADC087-00-VP

A National Institutes of Health vaccine in development for Marburg virus has first-in-human data showing it induced antibodies against this pathogen that causes a potentially deadly infection with no approved treatments. The data are from a small Phase 1 study. But the results are a step toward a vaccine for Marburg, a virus that comes from the same virus family as Ebola and causes similar hemorrhagic fever symptoms. The study results were published recently in the journal The Lancet. The NIH vaccine candidate, called cAd3-Marburg, was developed at the National Institute of Allergy and Infectious Disease’s Vaccine Research Center. It uses a modified chimpanzee adenovirus called cAd3 that can no longer replicate and cause infection. Engineered to display a protein found on the surface of Marburg virus, the vaccine is intended to induce an immune response to the pathogen. The vaccine platform on which cAD3-Marburg is based is the same technology the Vaccine Research Center used to develop experimental vaccines for Ebola virus and Sudan virus. The dose-escalation study, conducted at the Walter Reed Army Institute of Research Clinical Trials Center, enrolled 40 healthy adults. The first three participants received the low dose. When no adverse reactions were observed after seven days, the study proceeded to dose the next 17 participants. The same procedure was followed for the high dose. Results showed that the vaccine was well tolerated with no serious adverse events reported for either dose. A fever reported in one participant in the high dose group resolved the following day, the NIH said. On the measure of immune response, 95% of study participants exhibited a robust antibody response after vaccination, 70% of those participants maintained that response for more than 48 weeks. Last summer, a Marburg outbreak declared in Ghana ended following the implementation of outbreak control measures. Ghana is one of the countries where the NIH vaccine will face its next clinical tests. Other locations include Kenya, Ghana, and the U.S. If clinical data from those studies supports the promising results seen in the Phase 1 trial, the cAd3-Marburg virus vaccine could someday be used in emergency responses to Marburg virus outbreaks, the agency said. Image by Flickr user NIAID used under a Creative Commons license and cropped to fit publishing system requirements

A new article shows that an experimental vaccine against Marburg virus (MARV) was safe and induced an immune response in a small, first-in-human clinical trial. The vaccine could someday be an important tool to respond to Marburg virus outbreaks. A newly published paper in The Lancet shows that an experimental vaccine against Marburg virus (MARV) was safe and induced an immune response in a small, first-in-human clinical trial. The vaccine, developed by researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, could someday be an important tool to respond to Marburg virus outbreaks. This first-in-human, Phase 1 study tested an experimental MARV vaccine candidate, known as cAd3-Marburg, which was developed at NIAID's Vaccine Research Center (VRC). This vaccine uses a modified chimpanzee adenovirus called cAd3, which can no longer replicate or infect cells, and displays a glycoprotein found on the surface of MARV to induce immune responses against the virus. The cAd3 vaccine platform demonstrated a good safety pro prior clinical trials when used in investigational Ebola virus and Sudan virus vaccines developed by the VRC. MARV, a filovirus in the same family as Ebola virus, causes a rapidly progressive febrile illness that leads to shock and death in a large proportion of infected individuals. Many scientists think that MARV disease outbreaks in humans begin by when the virus makes the jump from its primary animal host, which is likely to be certain chronically infected bats in sub-Saharan Africa. The symptoms of MARV disease are akin to those seen with Ebola virus disease and can include fever, headache, chills, rash, abdominal pain, vomiting, and diarrhea. As the disease progresses, patients may suffer from multiple organ dysfunction, delirium, and significant bleeding from the gastrointestinal tract or other sites that may result in death. No approved vaccines or specific therapies are available for MARV disease, aside from supportive care. While some experimental vaccines have previously been tested, none have proven to be both highly effective and to provide durable protection. In areas of Africa where a vaccine for Marburg is most needed, a single-dose vaccine that could protect recipients over a long period of time would be a crucial part of quelling outbreaks. In this study, 40 healthy adult volunteers were enrolled at the Walter Reed Army Institute of Research Clinical Trials Center in Silver Spring, Maryland. They received a single dose of either a low dose of the vaccine (1x1010 particle units) or a higher dose (1x1011 particle units). For safety, the volunteers were enrolled in a dose-escalation plan. Three participants received the lower dose. Then, when they did not exhibit severe adverse reactions after the first seven days, the trial proceeded to enroll the remaining 17 volunteers. The same procedure was also used for the higher dose group. Volunteers were monitored for adverse reactions to the investigational 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 higher dose group developed a fever following vaccination, but it resolved by the following day. In addition, the investigational vaccine appeared to induce strong, long-lasting immunity to the MARV glycoprotein: 95% of participants in the trial exhibited a robust antibody response after vaccination, and 70% maintained that response for more than 48 weeks. Plans are in place to conduct further trials of the cAd3-Marburg vaccine in Ghana, Kenya, Uganda, and the United States. If additional data supports the promising results seen in the Phase 1 trial, the cAd3-Marburg virus vaccine could someday be used in emergency responses to MARV outbreaks.