A small clinical study overseen by the National Institute of Allergy and Infectious Diseases (NIAID) with support from the Frederick National Laboratory for Cancer Research has found that an experimental treatment for Middle East Respiratory Syndrome (MERS), an illness for which there is no licensed vaccine or treatment, is safe and well-tolerated in healthy volunteers. The study is also the first to demonstrate the safety of a treatment using antibodies manufactured from the plasma of cattle.
MERS, an upper respiratory infection with a high fatality rate, is a new to humans, first appearing in Saudi Arabia in 2012. According to the U.S. Centers for Disease Control and Prevention, about 3 to 4 out of every 10 patients reported with MERS have died.
Only two patients in the United States have ever tested positive for MERS, and so far, all cases of MERS have been linked through travel to or residence in countries in and near the Arabian Peninsula. However, MERS has spread through close contact, such as caring for or living with an infected person. Most MERS patients have developed severe acute respiratory illness with symptoms of fever, cough, and shortness of breath.
“The scenario you worry about is that someone becomes infected in Saudi Arabia, they aren’t symptomatic, and then they fly back to the United States and show up in Washington D.C. where the virus can spread,” said John Beigel, M.D., medical affairs scientist, Frederick National Lab, and lead associate investigator on the study. “Part of the planning is anticipating these risks and to advance our ability to treat MERS.”
Passive immunotherapy has been studied as a potential treatment for MERS and other emerging infectious diseases. It is an approach where antibodies produced outside of the body are given to patients to provide immunity against a disease or help fight off an infection. However, for diseases like MERS, it is a slow, small-scale process to harvest antibodies from human donors as they can only be taken from recently infected or vaccinated people.
For this phase I study, Beigel led a team of researchers in the execution of a clinical trial that used human antibodies manufactured in transchromosomic cattle, whose genes have been altered to enable them to produce human antibodies. The cattle are then immunized, in this case against MERS, and plasma is collected to make the antibody preparation. The treatment, called SAB-301, can be manufactured rapidly on a large scale because the plasma can be collected in larger quantities from cattle than from humans.
“We are trying to develop an antibody based therapy, and using this platform will make it much easier,” Beigel said. “To rely on harvesting human antibodies for a rare disease like MERS is not practical.”
For the study, 38 healthy volunteers participated, with 28 people treated with SAB-301 and 10 with a placebo. The participants were assessed closely several times throughout the study, and complaints among the treatment group were similar and generally mild, ranging from headaches to common cold symptoms. The researchers determined that single infusions of SAB-301 up to 50mg/kg were safe and well-tolerated in healthy participants. The research group’s findings were published in Lancet Infectious Diseases.
The next step is a larger phase II study in a population that is infected with MERS, which could demonstrate that the SAB-301 treatment is safe in that population and begin to evaluate whether the treatment is effective. Planning for the phase II study is underway.
In addition to Beigel, the team of researchers who conducted the phase 1 study were affiliated with NIAID, Department of Defense Naval Medical Research Center, and SAB Biotherapeutics, Inc.
By Max Cole, staff writer.
Image: Transmission electron micrograph of Middle East respiratory syndrome coronavirus. Credit: NIAID