Marburg virus vaccine safe in small, first-in-human clinical trial: NIH

By The Science Advisory Board staff writers

January 30, 2023 -- A study published in the Lancet on January 28 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 (NIH), could someday be an important tool for responding to MARV outbreaks, NIH said.

The World Health Organization (WHO) has identified MARV as an emerging virus requiring urgent vaccine research and development, particularly due to its recent emergence in Ghana, the study authors noted. 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 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 similar to those seen with the Ebola virus 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, aside from supportive care, are available for MARV disease. While some experimental vaccines have previously been tested, none have proven to both be highly effective and provide durable protection.

This first-in-human, Phase 1 study tested an experimental MARV vaccine candidate, cAd3-Marburg, which was developed at NIAID's Vaccine Research Center (VRC).

According to the NIH, the 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 profile in prior clinical trials, the NIH said, when used in investigational Ebola virus and Sudan virus vaccines developed by the VRC.

In areas of Africa where a vaccine for MARV 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 the Lancet study, 40 healthy adult volunteers were enrolled at the Walter Reed Army Institute of Research Clinical Trials Center in Silver Spring, MD. They received a single dose of either a low dose of the vaccine or a higher dose. For safety, the volunteers were enrolled in a dose-escalation plan. Three participants received the lower dose. When they did not exhibit severe adverse reactions after the first seven days, the trial then 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, the NIH said. 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 U.S. 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, the NIH added.

"These findings represent a crucial step in the development of a vaccine for emergency deployment against a re-emerging pathogen that has recently expanded its reach to new regions," the authors wrote.

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