Most people's first thoughts upon hearing mention of the Ebola or Marburg hemorrhagic fever viruses is that these are highly contagious, lethal, and have few established prevention, treatment, and cure measures.
Scientists whose work centers on diseases caused by filoviruses such as Ebola or Marburg are required to wear protective gear and remain in a restricted area designed with biocontainment precautions at the highest level to prevent contagion.
These working conditions describe the biosafety laboratory level 4 or BSL-4 lab located at Texas Biomed. The San Antonio-based BSL-4 lab was the first to be built west of the Mississippi and is the only civilian run BSL-4 lab in the U.S.
The Rivard Report toured Texas BioMed's lab facilities and spoke with Dr. Andrew Hayhurst in the Department of Virology and Immunology about his research and the BSL4 lab, which enables the work to be conducted safely. Hayhurst works on selected Tier 1 biothreat agents – diseases with the potential to pose a severe threat to human, animal, and/or plant health.
The team of scientists in Texas BioMed’s virology and immunology department focuses on developing vaccines, therapeutics, and tests for diseases including Ebola, Marburg, HIV, tuberculosis, and more recently, the Zika virus. The group collectively uses BSL-2, 3, and 4 laboratories to safely study these biological threat agents.
Hayhurst’s team has developed novel antibody engineering approaches to rapidly identify virus specific antibodies that can be reformatted into sensitive tests and new therapeutic avenues. These antibodies are based on a subset of llama antibodies known for their heat stability.
By developing rugged countermeasures that do not require refrigeration, diagnostic and therapeutic programs can eventually be implemented in resource-poor areas of the world with limited electricity and refrigeration – places where Ebola and Marburg viruses are endemic.
Texas BioMed's research is also focused on trying to understand why llama antibodies recognize parts of Marburg and Ebola viruses that conventional antibodies produced with mice or human tissue cannot. Hayhurst's team is collaborating with Dr. Alex Taylor and Dr. John Hart at UTHSCSA in using X-ray crystallography to visualize the antibody binding to a virus component of interest.
“We can solve part of the Marburg virus structure only when it is bound by the llama antibodies as it is so unstable,” Hayhurst explained. “Think of this chunk of Marburg virus as shaped like an open baseball catcher’s glove. When the llama antibody docks exactly in the pocket of the glove it closes and holds on tight, stabilizing the complex.”
Once the scientists figured out the crystallization process for the filoviral nucleoprotein and understood how the antibody protein binds to the virus, they began applying the same process to the Ebola virus, another hemorrhagic fever filovirus in the same family as Marburg. Better binders mean more sensitive diagnostics and more effective therapeutics and drugs.
“What’s really cool about these llama antibodies is that they hone in regions of the virus that never mutate, giving them huge potential for generations to come as the virus may not be able to evolve drug resistance,” Hayhurst added.
Origin of BSL-4 Lab at Texas BioMed
Dr. Jean Patterson, the first director and chair of the virology and immunology department, worked to establish the BSL-4 lab and explained to the Rivard Report how the BSL-4 lab came to be built at Texas BioMed.
“The original reason for the BSL4 was to enable a program working on herpes B, which is a level 4 pathogen,” Patterson said. “It’s potentially lethal, there’s no vaccine, there’s no treatment, and it can be transmitted in a lab – all criteria for doing the lab work in a BSL-4 lab.
“At that time in 1996, we only had a glove box (for lab work on infectious agents). If we’re building a new building, we should also build a BSL-4 to allow us to work with pathogens like herpes B.”
Patterson reflected on how the limited budget for the BSL-4 lab – due to a lack of federal funding – meant the lab was built with a streamlined design. That simple design has been the 1,200 sq. ft. lab’s strength, as it has lasted a long time with few maintenance issues.
“We would not have grown to the capacity we are now without it,” Patterson added.
The BSL-4 lab differentiates San Antonio from other centers of bioscience excellence, as it enables research on the most virulent pathogens.
“Perhaps because of the long history of our military population here in San Antonio, there is an understanding for the need for this kind of research and an appreciation of the risks and benefits,” Hayhurst said. “We’ve always encountered strong support here (for the BSL-4 and its research), and it is so encouraging for us all.”
Texas BioMed’s Primate Research Center
While primates have been at Texas Biomed since the 1950s, the National Institutes of Health awarded Texas BioMed funding in 1999 to establish its own Southwest National Primate Research Center, one of only seven National Institutes of Health National Primate Research Centers.
Because of their similarities to humans in genetics and physiology, nonhuman primates fulfill a unique and critical role in efforts that further the understanding of human health and disease. By studying these animals in a controlled environment, scientists can develop a better grasp on the biological processes that underlie and contribute to disease. They can then use this information to develop new, more effective ways to prevent and treat disease for the benefit of both humans and animals.
The Rivard Report visited the primate research center to preview one of the tours that will be available to participants traveling to San Antonio for the National Science Writers Conference that started Oct. 29. The Texas BioMed tour will feature time with Hayhurst to discuss his research, time with scientist and vice chair of Texas Biomed’s genetics department Dr. Laura Cox, as well as a tour of the Southwest National Primate Research Center.
“Texas BioMed is the only institute of its kind in the country, with two extraordinary resources in one place – the biosafety level 4 facilities and nonhuman primate colonies,” stated Dr. Robert Davey, chair of the department. “These resources allow for collaboration, quality control, and efficiencies that no other research center can offer.”
The scientific expertise, the BSL-4 laboratory, and the primate research center at Texas BioMed helps put San Antonio on the national map for scientists interested in Tier 1 agent research.
“There would not have been an Ebola vaccine response available without the (9/11) anthrax attacks,” Patterson said. “With the anthrax attacks came biodefense federal funding to work on emerging diseases that could be used offensively.”
With these three unique differentiators – scientists with specialized expertise, the BSL-4 lab, and co-located primates for testing therapeutics – the research on virulent and often fatal diseases can continue to grow as a vital part of San Antonio’s bioscience ecosystem.