The molecular events that affect disease transmission and human response to Ebola and Marburg viruses are poorly understood. Researchers in the NIAID Division of Intramural Research (DIR) and Vaccine Research Center (VRC), as well as NIAID-supported scientists at external institutions, are studying all aspects of the Ebola and Marburg viruses and how they cause disease. This includes seeking better ways to diagnose and treat Ebola virus disease and Marburg fevers and using applied research to develop diagnostics, vaccines, and treatments.
NIAID is supporting the development of multiple Ebola vaccine candidates that are in various stages of development.
The VRC developed an Ebola vaccine candidate in collaboration with the U.S. Army Medical Research Institute of Infectious Diseases and Okairos, a Swiss-Italian biotech company acquired by GlaxoSmithKline (GSK) in 2013. Known as the NIAID/GSK investigational Ebola vaccine, the candidate vaccine is based on a type of chimpanzee cold virus, called chimp adenovirus type 3 (cAd3). The adenovirus is used as a vector, or carrier, to deliver Ebola genetic material. The vector is a non-replicating viral vector, which means the vaccine delivers the gene inserts but does not replicate further. The gene inserts express a protein designed to prompt the human body to make an immune response. The investigational vaccine contains no infectious Ebola virus material.
When tested in Phase 1 clinical trials in the United States and the United Kingdom in 2014, the NIAID/GSK investigational Ebola vaccine proved to be safe and induced an immune response. The vaccine candidate is now being tested in the Partnership for Research on Ebola Vaccines in Liberia (PREVAIL) Phase 2/3 trial. In late March 2015, initial results from the Phase 2 portion of the PREVAIL trial involving more than 600 study volunteers indicated that the vaccine is safe. Plans are underway to begin Phase 3 testing of the vaccine.
NIAID has also been involved in testing the VSV-ZEBOV Ebola vaccine candidate. The vaccine uses a genetically engineered version of vesicular stomatitis virus, an animal virus that primarily affects cattle, to carry an Ebola virus gene segment. The investigational vaccine was developed by the Public Health Agency of Canada and licensed to NewLink Genetics Corporation. Merck & Co., Inc., is responsible for advancing the vaccine toward regulatory approval.
In Phase 1 testing conducted by NIAID and the Walter Reed Army Institute of Research, the VSV-ZEBOV investigational Ebola vaccine proved to be safe and elicited robust antibody responses in all 40 of the healthy adults who received it. The investigational is currently being tested in the PREVAIL vaccine trial in Liberia.
The NIAID Division of Microbiology and Infectious Diseases supported the development and preclinical and clinical testing of an investigational vaccine regimen targeting multiple species of Ebola and Marburg viruses. The vaccine candidate is a prime-boost combination of an adenovirus vector platform in development at the Janssen Pharmaceutical Companies (Crucell) of Johnson & Johnson and a modified vaccinia virus Ankara (MVA)-vectored vaccine developed by Bavarian Nordic. Johnson & Johnson is currently conducting Phase 1 clinical trials of the investigational vaccine regimen in Kenya, the United Kingdom, and the United States. NIAID is supporting the U.S. clinical trial.
Additionally, NIAID is funding Profectus Biosciences, Inc., to develop a recombinant vesicular stomatitis virus (VSV)-vectored vaccine against Ebola and Marburg viruses. The vaccine is in preclinical testing. Further, NIAID is working with the Galveston National Laboratory & Institute for Human Infections and Immunity at the University of Texas Medical Branch at Galveston to advance progress made by NIAID intramural scientists on a paramyxovirus-based vaccine against Ebola.
NIAID intramural scientists are collaborating with Thomas Jefferson University investigators to produce a vaccine candidate based on an existing rabies vaccine that would protect against Ebola, Marburg, and rabies viruses. The scientists are pursuing a version of the vaccine for human and veterinary use, as well as a version for African wildlife. NIH licensed the candidate rabies/Ebola vaccines to Exxell BIO, which aims to advance the products through clinical testing and potential commercialization.
NIAID is supporting the development of a number of investigational Ebola treatments that are in different stages of development.
ZMapp, an investigational Ebola treatment developed by Mapp Biopharmaceutical Inc., is a “cocktail” of three different proteins, called monoclonal antibodies. The antibodies are produced in tobacco plants specifically bioengineered to produce large quantities of the proteins. When tested in nonhuman primates, ZMapp demonstrated strong antiviral activity and rescued the animals from death as late as five days after infection with Zaire Ebola virus. The investigational treatment was administered under emergency use authorization to Ebola-infected patients in Africa, the United States, and Western Europe. It is now being tested in a clinical trial in Liberia and the United States. NIAID, which supported the earlier development and preclinical testing of Zmapp, is conducting the clinical study in partnership with the Liberian government.
Additionally, through the NIAID Centers of Excellence for Translational Research program, Erica Ollmann Saphire, Ph.D., of Scripps Research Institute, leads a consortium to study immunotherapeutics against viral hemorrhagic fevers which identified ZMapp’s structure and how it binds to Ebola virus. Dr. Saphire is using this knowledge to test next-generation antibodies for better binding and efficacy.
BCX4430, developed by BioCryst Pharmaceuticals, is an investigational small molecule drug with broad spectrum antiviral activity, including against Ebola. BCX4430 has protected animals against infection with Ebola and Marburg viruses. NIAID is supporting development and testing of the investigational Ebola treatment in nonhuman primates as well as human clinical safety trials. A Phase 1 study of the drug candidate began in the United Kingdom in late 2014.
NIAID is also supporting the development of improved diagnostics to detect Ebola virus infection, including those that can provide rapid identification and can be deployed at the point-of-care where Ebola outbreaks occur. For example, since 2005 NIAID has supported BioFire Diagnostics in developing FilmArray, a multiplex polymerase chain reaction (PCR) system. Initial NIAID support focused on the development of FilmArray’s Respiratory Panel, which can simultaneously detect 20 respiratory viruses from patient samples in one hour. Efforts were expanded to include a Blood Culture Identification Panel and a Gastrointestinal Panel. NIAID provided partial support to develop an Ebola diagnostic for the FilmArray instrument, which was granted emergency use authorization by the Food and Drug Administration (FDA) in October 2014.
Additionally, with NIAID support, Corgenix Medical Corporation’s rapid immunodiagnostic for Ebola viruses—the ReEBOV Antigen Rapid Test Kit—became eligible for World Health Organization procurement and FDA emergency use authorization in February 2015. The diagnostic can provide results within 15 minutes and is based on direct detection of an Ebola protein, rather than amplification of nucleic acids. NIAID also is advancing development of other types of diagnostics, including those using novel technologies, such as microfluidics, optofluidics, and nanophotonics, which are capable of detecting an array of viruses, including Ebola viruses.
Through the NIAID-funded Genomic Sequencing Center at the Broad Institute, NIAID is supporting the sequencing and comparative genomic analysis of Ebola virus isolated from patients infected in the 2014–2015 Ebola outbreak in West Africa. Led by the Broad Institute's Dr. Pardis Sabeti, researchers have sequenced the genomes of more than 570 human clinical samples. This work has provided critical information about the genetic composition and variation of Ebola virus circulating in West Africa. NIAID made this data rapidly available to the scientific community by submitting it to the public database GenBank. NIAID is also supporting the access and analysis of this data through its ViPR Bioinformatics Resource Center, which provides easy access to publicly available Ebola genomic sequences, clinical data associated with the samples and data analysis tools.
Additionally, NIAID provides preclinical services, such as drug screening and animal testing, to researchers in academia and industry to advance vaccine and treatment product development. NIAID established and conducted a responsive vaccine screening capability that provided essential early proof-of-concept efficacy data in nonhuman primates that was instrumental in rapidly advancing some vaccine candidates into clinical testing.
More than 30 different filovirus vaccine formulations have been evaluated through NIAID preclinical services since 2011 using animal models and assays that NIAID developed over many years. Several of these candidates qualified for further testing, and a number are currently in the product development pipeline. NIAID has also screened licensed drugs for anti-filovirus activity to gauge their potential as Ebola treatments.
Last Updated April 15, 2015