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A Faculty’s Take On EBOLA

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One focus of Dr. Hayhurst's laboratory is Ebola, so we asked him to share his thoughts with us!

Author: Andrew Hayhurst, PhD | Category: Of Interest | Infection, Inflammation & Immunity (Triple-I) | Infection, Inflammation, and Immunity | August 07, 2014

News coverage has been fairly extensive and it is now nice to see some more in depth commentaries as to why this particular Ebola virus outbreak has become so large. These war-torn areas have suffered severe neglect in terms of healthcare expenditure, education and infrastructure for many decades such that a transmissible lethal disease can take a real foothold in a human population. 

It’s also come as quite a surprise that Ebola has emerged so vigorously in this part of Africa since the last incidence in ‘94/’95 involved 2 non-fatal cases of a different species of Ebolavirus (Ivory Coast or Taï Forest ebolavirus). Thus, unlike Gabon and the Congos where Ebola virus outbreaks are more frequent, people in West Africa had little to no awareness of the disease, how to avoid infection and how to break the transmission cycle. In resource poor areas, protein can be hard to come by and so reliance on hunting bushmeat (potentially infected with Ebola virus) from the forests can pose a particular risk for the local population. It’s also interesting that the more recent news coverage is raising questions about the financial logistics and drive of getting vaccines and therapeutics for neglected tropical diseases into human clinical trials. 

If Ebola wasn’t considered a Tier 1 potential bioweapon with a lot of funding coming from the DoD and NIAID for countermeasures, I’m not sure there would be much of anything in the pipeline to offer as the larger pharma companies often shy away from products with low profit margin. The daily ProMED-email is also a very good way to keep up with the Ebola outbreak and many other interesting disease emergences, even animal and plant diseases… makes the early morning coffee more interesting if a little depressing on occasion.

While in the Republic of Congo as a guest of the National Health Laboratory in Brazzaville some time ago I saw that bats are available from market traders for consumption (bats are reservoir hosts for many emerging viruses including Marburg, a close relative of Ebola). 

On the way North to the forests and previous outbreak areas there are signs erected as part of the health education system to increase Ebola awareness. The system they have established with visits to villages, graphic flipcharts, posters and discussion communicates the potential danger of butchering forest animals, and the basics of infection control and safe burial practices should someone become sick and die.

As part of the ASM Biodefense and Emerging Diseases Research Meeting committee I organized a session this past January with Larry Zeitlin to highlight advances in plant based production strategies for therapeutics and vaccines. Larry is president of Mapp Biopharmaceutical Inc. the source of the cocktail of plant made Ebola neutralizing antibodies administered to the two infected healthcare workers recently returned to the US. The study of anti-Ebola “plantibodies” has been developing with Gene Olinger (who was one of our speakers), Gary Kobinger and several other collaborators in the US and Canada to demonstrate successful resolution of an Ebola virus infection in non-human primates.

It’s terrific to see a technology that was one on the relative fringe of pharma show its potential to produce complex products at industrial scale at a fraction of the cost of conventional mammalian expression systems, and at a much faster pace. It was a super little session and caught the eye of ASM Microbe Magazine to get a write up in the June edition. 

We’re always very interested in Filovirus outbreaks and countermeasures of one sort or another as we are developing novel assays and interventions for biothreat agents and trying to accelerate and simplify their generation.

We’ve been focusing on new ways to accelerate the assembly of antigen capture assays using llama single domain antibodies that are more heat stable than conventional IgG and offer the prospect of cold-chain free tests. We’ve tackled the world’s “most poisonous poisons” (botulinum neurotoxins), 

Ebola viruses and Marburg virus to pathfind the llama systems. We’re also interested in basic science questions, how and why synthetic antibodies recognize certain highly conserved regions of their viral target antigens. In collaboration with Alex Taylor and John Hart at the X-ray crystallography lab at UTHSCSA we’re working out these mechanisms for Marburg and moving on to Ebola using harmless recombinant protein surrogates. We’re very lucky to have a BSL-4 or space-suit lab here at Texas Biomed to work with the live viruses themselves, selecting binders against native protein conformations, and testing our ideas out.

Ebolavirus Nucleoproten C-Termini Potently Attract Single Domain Antibodies Enabling Monoclonal Affinity Reagent Sandwich Assay (MARSA Formulation

Hapten Mediated Display and Pairing of Recombinant Antibodies Accelerates Assay Aseembly for Biothreat Countermeasures

Llama Single Domain Antibodies Specific for the 7 Botulinum Neurotoxin Serotypes as Heptaplex Immunoreagents

Team in the BSL-2, (left to right) Larissa Muhlenbeck (PROMOS intern from University of Bonn, Germany), Tamarand Lee Darling (Microbiology and Immunology graduate student, UTHSCSA), me, Laura Jo Sherwood (Senior Research Associate), Divya Nandamudi (Microbiology and Immunology graduate student, UTHSCSA)

Photos © A.H



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