Synthetic antibodies may protect against Ebola

Scientists have engineered novel antibodies that may effectively protect against Ebola virus.

A study, published in the journal Cell Reports, showed that the DNA-encoded monoclonal antibodies (DMAbs) were expressed over a wide window of time and offered complete and long-term protection against lethal virus challenges.

According to the scientists from The Wistar Institute in the US, DMAbs may also provide a novel powerful platform for rapid screening of monoclonal antibodies enhancing preclinical development.

Ebola virus infection causes a devastating disease, known as Ebola virus disease, for which no licensed vaccine or treatment are available. The 2014-2016 Zaire Ebola virus epidemic in West Africa was the most severe reported to date, with more than 28,600 cases and 11,325 deaths according to the US Center for Disease Control.

A new outbreak is ongoing in the Democratic Republic of Congo, with a death toll of more than 200 people since August.

One of the experimental avenues scientists are pursuing is evaluating the safety and efficacy of monoclonal antibodies isolated from survivors as promising candidates for further development as therapeutics against Ebola virus infection.

However, this approach requires high doses and repeated administration of recombinant monoclonal antibodies that are complex and expensive to manufacture, so meeting the global demand while keeping the cost affordable is challenging.

"Our studies show deployment of a novel platform that rapidly combines aspects of monoclonal antibody discovery and development technology with the revolutionary properties of synthetic DNA technology," said David B Weiner, from Wistar Institute.

The team designed and enhanced optimised DMAbs that, when injected locally, provide the genetic blueprint for the body to make functional and protective Ebola virus-specific antibodies, circumventing multiple steps in the antibody development and manufacturing process.

Dozens of DMAbs were tested in mice and the best-performing ones were selected for further studies. These proved to be highly effective for providing complete protection from disease in challenge studies.

"Due to intrinsic biochemical properties, some monoclonal antibodies might be difficult and slow to develop or even impossible to manufacture, falling out of the development process and causing loss of potentially effective molecules," said Weiner.

"The DMAb platform allows us to collect protective antibodies from protected persons and engineer and compare them rapidly and then deliver them in vivo to protect against infectious challenge," he said.

"Such an approach could be important during an outbreak, when we need to design, evaluate and deliver life-saving therapeutics in a time-sensitive manner," he added.