Credit: National Institutes of Health
Updated Oct. 22, 2014: The National Institutes of Health (NIH) today announced the start of human clinical trials of a second Ebola vaccine candidate at the NIH Clinical Center in Bethesda, MD. In this early phase trial, researchers from NIH’s National Institute of Allergy and Infectious Diseases (NIAID) are evaluating the vaccine, called VSV-ZEBOV, for its safety and ability to generate an immune response in healthy adults who receive two intramuscular doses, called a prime-boost strategy.
The Walter Reed Army Institute of Research is simultaneously testing the vaccine candidate as a single dose at its Clinical Trials Center in Silver Spring, MD. VSV-ZEBOV, which was developed by researchers at the Public Health Agency of Canada’s National Microbiology Laboratory, has been licensed to NewLink Genetics Corp. through its wholly owned subsidiary BioProtection Systems, both based in Ames, Iowa.
Early human testing of another Ebola vaccine candidate, co-developed by NIAID and GlaxoSmithKline, began in early September at the NIH Clinical Center. Initial data on that vaccine’s safety and ability to generate an immune response are expected by the end of 2014.
We are all alarmed by the scope and scale of the human tragedy occurring in West African nations affected by the Ebola virus disease epidemic. While the cornerstones of the Ebola response remain prompt diagnosis and isolation of patients, tracing of contacts, and proper protective equipment for healthcare workers, the National Institutes of Health (NIH), led by its National Institute of Allergy and Infectious Diseases (NIAID), is spearheading efforts to develop treatments and a vaccine for Ebola as quickly as possible.
For example, NIAID has supported and collaborated with Mapp Biopharmaceutical, Inc., San Diego, in its development of the product known as ZMapp, which has been administered experimentally to several Ebola-infected patients. While it is not possible at this time to determine whether ZMapp benefited these patients, NIAID is supporting a broader effort to advance development and clinical testing of ZMapp to determine if it is safe and effective. In addition, the U.S. Biodefense Advanced Research and Development Agency (BARDA) has announced plans to optimize and accelerate the manufacturing of ZMapp, which is in limited supply, to enable clinical safety testing to proceed as soon as possible.
NIAID is also supporting the development of other potential treatments. Among them is BCX4430, a drug that BioCryst Pharmaceuticals, Research Triangle Park, NC, plans to enter into a Phase 1 human clinical trial by early 2015. Another potential drug, brincidofovir, developed by Chimerix of Durham, N.C., has been evaluated in more than 1,000 patients for two non-Ebola viruses (cytomegalovirus, adenovirus). Brincidofovir has shown some ability to suppress Ebola viruses in cell cultures, and was recently administered to several patients with Ebola virus disease. Again, while it is impossible to determine on the basis of a few patients whether a drug is effective against Ebola, brincidofovir appears to be safe in humans. Broader evaluation of the drug will likely take place in the coming months.
In addition, the HIV drug, lamivudine, has also been used in some Ebola patients in Liberia, under the supervision of a Liberian physician. Cell culture testing of the drug is being conducted in the United States, and if promising, clinical trials could be performed.
A safe and effective Ebola vaccine could be a critically important tool to help prevent Ebola virus infection and help contain the present and future outbreaks. Several Ebola vaccine candidates are undergoing Phase 1 human clinical testing this fall after proving effective in animals. One of these is a vaccine candidate developed by NIAID and GlaxoSmithKline, London; this product entered a small Phase 1 study at the NIH Clinical Center in Bethesda, MD, last month, and the study is now expanding to additional sites.
Additionally, NIH will collaborate with the Department of Defense and NewLink Genetics Corp., Ames, IA, on Phase 1 human safety studies of another investigational Ebola vaccine candidate, which was developed by and licensed from the Public Health Agency of Canada. Other vaccine candidates are in earlier stages of development in animal models. Knowledge gained through all of these studies will further the goal of deploying a safe and effective vaccine that will prevent this deadly disease.
During this extremely serious outbreak of Ebola virus disease in West Africa, we must balance the urgent desire to deploy experimental countermeasures with the need to ensure safety and determine the efficacy of the products. We would not want to introduce products, particularly preventive measures for healthy, uninfected individuals, if they are ineffective or even harmful.
Randomized, controlled clinical trials remain the “gold standard” for the evaluation of candidate drugs and vaccines because they represent the most efficient way to prove efficacy and safety. This is an imperative for any intervention delivered to healthy individuals. As we proceed through clinical testing, NIH will continue to work with our partners at BARDA, the Food and Drug Administration (FDA), and elsewhere to accelerate efforts to develop and provide access to Ebola vaccines and treatments in a manner that is both scientifically and ethically sound.
Note: Anthony S. Fauci, M.D., is Director of the National Institute of Allergy and Infectious Diseases (NIAID), NIH
Links:
Understanding Ebola and Marburg hemorrhagic fevers (NIAID)
Ebola/Marburg Research (NIAID)
Ebola–underscoring the global disparities in health care resources.
Fauci AS. N Engl J Med. 2014 Sep 18;371(12):1084-6.
Ebola Virus Disease (CDC)
CDC: Stopping the Ebola Outbreak
NIH support: National Institute of Allergy and Infectious Diseases