1. “28,424 cases of Ebola and still counting—what have we learned
“28,424 cases of Ebola and still counting—what have we learned?” AAMC Briefing
Dr. Jim LeDuc
Director
Galveston National Laboratory
University of Texas Medical Branch
13 October 2015

2. GNL Mission
The mission of the GNL is to assist the NIAID and the nation by conducting basic and applied research designed to improve the prevention, diagnosis and treatment of naturally emerging and purposefully disseminated infectious diseases.
Opened in 2008; fully commissioned and operational since 2010
About 300,000 sq ft of laboratory, mechanical and office space—equivalent to most federal biocontainment labs
Vision is to bring the strengths in basic and translational research found in academic centers to the challenges of emerging infectious diseases and threats of bioterrorism

3. From bench to bedside… Basic Research Product Development
NIH R01 and other Funded Research
Proof of Concept
Concept Validation
Pre-clinical/ GLP Studies
Human Clinical Trials
Animal Rule
Traditional basic research funded primarily by NIH
Translational research funded by NIH, DOD and others, including the commercial sector
Focus on Preclinical testing to advance promising candidates to human trialsAnimal Rule
Phase I:
Safety
Phase II: Expanded Safety
Phase III:
Efficacy
FDA
Restricted Use Approval
GNL
UTMB
FDA Licensure

4. Impact of Research on Ebola
Important research moved through preclinical phases, into clinical trials, and to patients.
ReEBOV Rapid Diagnostic Test for Ebola – commercialized and in use in West Africa.
siRNA post-exposure treatment for Ebola went to Phase 1 and Phase 2 clinical trials.
Zmapp (human monoclonal antibodies therapy) clinical trials and applications.
rVSV (recombinant vesicular stomatitis virus) vaccine trials in Africa and Europe.
Adenovirus vectored vaccine trials.
Ebola epidemic called to action decades of research on Ebola and related viruses
Adenovirus vectors vaccine started in mid-1990’snow in NIH sponsored human trials in West Africa
rVSV vaccine started in early 2000’snow most promising vaccine following demonstrated efficacy in “ring vaccination trial” in Guinea.
Zmapp validated in animal trials at UTMB; used clinically in US cases
siRNA effective in animal testing at UTMB; advanced to human trials in West Africa; trials terminated
Diagnostic assays rapidly developed based on access to live Ebola virus and specimens from acutely ill animals used in vaccine and drug development

5. Current status of rVSV vaccine
April 2015
An important questions was, will the vaccines and diagnostics under development work against the new West African strain of Ebolaonce the virus was available, this was quickly answered and the results shared internationally.
August 2015
Efficacy and effectiveness of an rVSV-vectored vaccine
expressing Ebola surface glycoprotein: interim results from
the Guinea ring vaccination cluster-randomised trial ,

6. Rapid Test for Ebola
15 min rapid screening assay using whole blood from finger prick
Produced by Corgenix (Broomfield, Colorado)
Uses antibodies to identify specific Ebola virus protein
Anticipated cost about $15/test
92% of infected people identified; 85% of uninfected—confirmation by PCR
Approved by FDA and WHO
Rapid test for Ebola developed and utility confirmed in laboratory testing at UTMB using live virus and specimens from animals involved in vaccine and drug testing
NEXT SLIDE

7. Team from UTMB and others validated the rapid test on the ground in Kenema, Sierra Leone, at the height of the epidemic using clinical material from acutely ill patients
Test quickly approved by FDA and WHO

8. Cepheid EBOV Diagnostics
Collaboration with Cepheid initiated October 2014 in response to West Africa EBOV outbreak; Cepheid has footprint in Africa for Tb work.
Worked with Cepheid to build EBOV specific diagnostic test
Tested limit of detection (LoD) for EBOV RNA and live EBOV virus
Participated in mock clinical study which led to Cepheid receiving emergency use authorization (EUA) to use diagnostic in the West Africa outbreak
EUA received by March 2015 through working with UTMB at the GNL.
Progress: From no product in October 2014 to diagnostic test used in Africa under EUA by March 2015.
10 minutes
~90 minutes
A second diagnostic test developed in partnership with Cepheid, a biotech firm with an established global network of partners already testing for important diseases of public health concern like TB
Benefit is that this test builds on existing technology and is already in use globally. By including Ebola testing capabilities, we are enhancing the sustainability of diagnostic testing for this rare but extremely important disease.

9. Unique Strengths of Academic Medical Centers
Highly trained experts in their field.
Cutting edge knowledge of current advances, including unpublished work in progress.
Immediate access to reference pathogens and reagents.
Through the NIH network, access to appropriate biocontainment laboratories.
Skilled workforce approved to handle select agents.
State-of-the-art equipment and instrumentation.
Appropriate biosafety and biosecurity training—skills being passed on to clinicians.
Rapid test for Ebola developed and utility confirmed in laboratory testing at UTMB using live virus and specimens from animals involved in vaccine and drug testing
NEXT SLIDE

10. Conclusions
The health of the nation is intimately intertwined; an outbreak anywhere is a threat everywhere—pathogens don’t carry passports!
Some of today’s health threats—like Ebola—are extremely dangerous and require highly specialized facilities and skilled personnel to develop the drugs and vaccines needed to protect the nation.
The investments by NIH have created a network of biocontainment laboratories on academic medical centers that fosters innovation and discoveries to address the most dangerous global threats to health.
Challenges going forward include sustained funding to support basic and translational research in these specialized facilities, and a regulatory environment that fosters collaboration and innovation.

11. Thank You. For more information: www. utmb
Thank You! For more information: Jim LeDuc
Opened in 2008; fully commissioned and operational since 2010
About 300,000 sq ft of laboratory, mechanical and office space—equivalent to most federal biocontainment labs
Vision is to bring the strengths in basic and translational research found in academic centers to the challenges of emerging infectious diseases and threats of bioterrorism