While the Ebola epidemic rages on in West Africa, scientists around the world are continuing to search for better tools to diagnose and treat the disease. Current methods of diagnosis require lengthy testing procedures and the virus is often undetectable until viral load is very high, which doesn’t occur until after severe symptoms appear. The ability to diagnose the infection earlier will allow epidemiologists and health care workers on the ground to respond to an outbreak more quickly and therefore stop the epidemic in its tracks.
Researchers from San Antonio’s Texas Biomedical Research Institute have been awarded $2.36 million from the National Institutes of Health (NIH) to identify virus particles early in the infection. Many testing kits, medications, and vaccines require cold storage throughout transport – a “cold chain.” In a place without electricity, that cold chain is easily broken. The challenge, then, is to develop a test that is heat stable, maintaining its functionality without the need for refrigeration.
The lab of Dr. Andrew Hayhurst and Senior Research Associate Laura Jo Sherwood had long been investigating the use of engineered antibodies against severe pathogens. However, developing those antibodies naturally is a challenge: infecting a large animal with a highly pathogenic virus and waiting for specific antibodies to develop poses many safety issues. So they developed “naïve antibody libraries” which can be engineered to target specific viruses.
Enter the llama. A number of years ago a colleague with pet llamas offered some specimens to Dr. Hayhurst. His team used these to develop a naïve antibody library and found that these llama antibodies were heat stable – they didn’t need a cold chain. Finding them a bit useless for their purposes, they were about to throw them out.
At the same time, the lab had purified a bit of Marburg virus, another Filovirus closely related to Ebola virus. Filoviruses mutate rapidly, which is a problem for treatment and vaccine development, but also for testing. It is difficult to develop a testing tool that specifically targets the viral genome if it is constantly changing. But there is one small part of the genome that is highly conserved – the region involved in viral assembly.
They tested their llama antibodies against this conserved region of Marburg virus and found a match. An earlier, much smaller NIH grant allowed Hayhurst and his team to collaborate with Dr. Alex Taylor and Dr. John Hart of the UT Health Science Center X-ray crystallography core lab where they could visualize the structure of the viral regions targeted. This opened up the door – or the lab – for new possibilities in their research, identifying the keys to viral evolution.
The current grant will allow the group to study the ability of the llama antibodies to target other Filoviruses, such as Ebola. Ultimately, this research will enable scientists to develop testing kits that can be used in the field in settings with limited resources, which is where Ebola occurs.
Scientific discoveries involve a great deal of creativity, intense work, and brilliant insight. And sometimes it needs just a bit of serendipity – a friend with some llamas, perhaps.
*Featured/top image: Scientists at Texas Biomedical Research Institute work in the “hot zone” lab with highly lethal agents for which there are no vaccines or cures. Photo by Clem Spalding, courtesy of Texas Biomedical Research Institute.