Research conducted at the Texas Biomedical Research Institute in San Antonio to discover a quick Ebola diagnostic method as well as a method for limiting contamination and a possible outbreak was awarded a $2.36 million grant from the National Institutes of Health (NIH). The project intends to develop a new way of detecting Filovirus through the use of llama antibodies.
With the recent spread of the Ebola virus in several countries, a research team led by researcher Andrew Hayhurst started investigating the possibilities of diagnosis through the blockade of virus particles called polymeric proteins. Currently, the most effective diagnostic method is a specific genome test that examines viral DNA or RNA using polymerase chain reaction (PCR) amplification. However, during infection, specific antibodies created by the host as a consequence of viral infection can already be detected.
“Detecting single viral protein components can be challenging, especially at very low levels; however, most viruses are repetitive assemblies of a few components, with some existing as polymers of several thousand copies, which present great targets for our llama antibodies,” said Dr. Hayhurst in a press release. “If you consider one viral protein binding to one llama antibody the interaction can be relatively modest, but if you consider thousands of pairs of hooks as occurs in sheets of Velcro, the interaction between the two becomes much more powerful. A more powerful interaction leads to a more sensitive diagnostic,” added the researcher, referring to the “Mechanism and Evolution of Filoviral Monoclonal Affinity Reagent Sandwich Assays” study.
The team, which also includes researchers Alex Taylor and John Hart from UT Health Science Center X-ray crystallography core lab, wants to increase knowledge on the interaction mechanisms established by the llama antibody and the viral protein by studying the interface of atoms and understanding the mechanisms behind llama antibodies binding.
“We’ve had these beautiful structures for quite a while now generated with the help of former lab member Dr. John Garza, but I only appreciated the significance of them more recently when pondering viral evolution,” continued Hayhurst. “Examining all the strains of Marburg virus that have emerged since 1967, we can graft predicted mutations onto our crystal structures to indicate that our antibodies bind a highly conserved structure that has never changed.”
Since Ebola is an RNA virus, it can mutate and evolve, making it harder to detect without PCR or antibody-based tests, especially if these techniques cannot identify the latest virus strains. Researchers noted that despite the fact that llama antibodies do not correspond to the sensitivity of current qRT-PCR tests, they intend to develop improved tests.
“Our aim is to develop these llama antibodies into streamlined tests designed to detect all Marburg and Ebola strains known and potentially those yet to emerge. Our goal is to help to safeguard human health both now and into the future. Pioneering simple, fast and inexpensive llama antibody based Filoviral immunoassays that match qRT-PCR sensitivity and specificity, will help safeguard human health by providing a comprehensive diagnostic toolkit for outbreak settings,” added Hayhurst.
The Ebola outbreak has generated a serious discussion and work all over the country, in particular among Texas academics and institutions, since it is one of the deadliest viruses in the world, causing an acute, severe illness in humans. The U.S. Food and Drug Administration (FDA) also recently granted emergency use authorization to a new rapid test kit for the diagnosis of Ebola infection, called the ReEBOVTM Antigen Rapid Test.