A research team led by scientists at Vanderbilt University Medical Center has developed an antibody mixture that in animals is highly effective in blocking infection by the Ebola virus.
Reporting in the journal Immunity, these findings “could aid in the design of therapeutic cocktails against other viral targets,” the researchers concluded.
Ebola is a severe and often fatal hemorrhagic fever affecting humans that can be caused by four known Ebola viruses.
Previous attempts to develop combinations or mixtures of antibodies that are broadly cross-reactive to the predominant strains of Ebola have been constrained by limited understanding about how the antibodies “cooperate” in neutralizing the virus and by the cost and difficulty of the research.
Now James Crowe Jr., MD, and colleagues in the Vanderbilt Vaccine Center have identified a combination of two new antibodies that neutralize strains of the virus responsible for most of the recent, large-scale and highly fatal Ebola outbreaks in the Congo and West Africa.
As a first step, antibody-producing white blood cells were isolated from survivor blood samples and then fused to fast-growing myeloma (cancer) cells to produce large quantities of “monoclonal” antibodies targeting specific viral strains.
Pavlo Gilchuk, PhD, senior staff scientist in the Crowe lab, led the discovery efforts of a group of researchers from across the country.
They analyzed more than 1,800 human monoclonal antibodies and found two classes of broadly reactive antibodies that bind simultaneously and in a cooperative fashion to a protein on the surface of the virus called the glycoprotein which is conserved between viral strains.
When combined, the resulting two-antibody mixture neutralized the virus and protected mice and non-human primates against a live Ebola virus challenge.
Others from Vanderbilt who participated in the study were Robert Carnahan, PhD, associate director of the Vanderbilt Vaccine Center, Rachel Nargi, Robin Bombardi and Megan Vodzak.
The research was supported by the National Institutes of Health, U.S. Department of Health and Human Services, Defense Threat Reduction Agency, Defense Advanced Research Projects Agency (DARPA) and by the Bill and Melinda Gates Foundation.