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DNA-Encoded Synthetic Antibodies Protect Against Ebola

Ebola virus

Ebola virus (

14 Nov. 2018. Synthetic antibodies derived from survivors of Ebola infections are shown to be quick and simple to develop, and in lab mice to provide long-term protection against against Ebola viruses. Researchers from the Wistar Institute in Philadelphia and Inovio Pharmaceuticals in San Diego report their findings in yesterday’s issue of the journal Cell Reports.

A team led by immunologist David Weiner, director of the institute’s Vaccine & Immunotherapy Center, is seeking faster and easier methods to make vaccinations against the Ebola virus. A new Ebola outbreak is taking place in Democratic Republic of the Congo, which World Health Organization as of 12 November reports 301 confirmed cases and 174 deaths, with more probable cases and deaths likely. The 2014-15 outbreak in West Africa, according to WHO, reported more than 28,600 cases and 11,300 deaths.

From the previous outbreak, a number of treatment and vaccine candidates emerged, including a group of synthetic targeted antibodies developed by Mapp Biopharmaceutical known as ZMapp. These engineered antibodies were shown in lab animals and early experience with humans to protect against Ebola infections. However, patients required frequent high-dose infusions for the synthetic antibodies to remain effective, and current development and production methods were likewise slow and complex. It became clear to health authorities that more efficient processes were needed should another large-scale Ebola outbreak occurred.

One result of the earlier West Africa experience is more than 10,000 individuals who survived their infections. From their exposure to Ebola, these individuals likely developed natural antibodies against further infections. Weiner and colleagues captured some of these antibodies from survivors and combined them with ZMapp’s engineered antibodies to create new Ebola antibodies.

These DNA-encoded antibodies were created with a process that Inovio Pharmaceuticals licensed from Weiner’s lab while he was at University of Pennsylvania. In this process, called DMab — short for DNA monolclonal antibody — DNA fragments are ingested into cells, where they’re exposed to mild electrical pulses, called electroporation, that increases the uptake of DNA to generate more antibodies. Weiner is a scientific adviser to Inovio.

In September 2015, Science & Enterprise reported on a clinical trial of synthetic targeted antibodies developed with this process to clear up cervical lesions or sores before they become cancerous, which found women receiving the vaccine eradicated more of these lesions than those receiving a placebo.

In the new study, the researchers generated synthetic antibodies with viral DNA, which in lab mice protect against the Ebola virus. The team produced 26 types of DMabs that connected to specific binding targets, known as epitopes, on the virus. In tests with mice, one of the better performing DMabs protected the animals given the Ebola virus. After 82 days following exposure to Ebola, 40 percent of the mice continued to survive.

To counteract Ebola outbreaks, health authorities need to administer vaccines quickly to large populations. The researchers found their process could quickly produce DMabs, which they says is limited only by availability of the latest viral DNA from the scene. “The DMAb platform,” says Weiner in a Wistar statement, “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. 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.”

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