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 Ebola and Marburg viruses and how they cause disease. This includes seeking better ways to diagnose and treat Ebola and Marburg fevers, and using applied research to develop diagnostics, vaccines, and therapeutics.
The VRC has developed an Ebola vaccine candidate in collaboration with Okairos, a Swiss-Italian biotech company recently acquired by GSK. The investigational vaccine, which was designed by VRC scientists, contains no infectious Ebola virus material. It is a chimpanzee adenovirus vector vaccine into which two Ebola genes have been inserted. This is a non-replicating viral vector, which means the vaccine enters a cell, delivers the gene inserts and does not replicate further. The gene inserts express a protein to which the body makes an immune response. The investigational vaccine has recently shown promise in a primate model. The VRC vaccine will enter into a Phase I clinical trial, which could start enrollment as early as fall 2014, pending approval by the Food and Drug Administration. The VRC is also in discussions with governmental and non-governmental partners regarding options for advancing this candidate beyond Phase I clinical evaluation.
Additionally, the NIAID Division of Microbiology and Infectious Diseases is supporting the Crucell biopharmaceutical company’s development of a multivalent Ebola/Marburg vaccine using recombinant adenovirus vector platforms. A Phase I clinical trial is planned for late 2015 or early 2016. NIAID is also funding Profectus Biosciences to develop and test a recombinant vesicular stomatitis virus vectored vaccine against Ebola virus. The vaccine is currently in preclinical testing to determine the most promising constructs. In addition, NIAID is working with Bavarian Nordic on development of a recombinant Marburg vaccine candidate that uses the Modified Vaccinia Ankara vector.
Investigators from DIR and Thomas Jefferson University are collaborating to develop a candidate Ebola vaccine based on the established rabies virus vaccine that has demonstrated protection against rabies and Ebola infection in animals. This research team is pursuing an inactivated version of this vaccine for human and veterinary use and a live vaccine for use in wildlife in Africa to help prevent the transmission of Ebola virus from animals to humans.
NIAID is supporting a number of projects designed to develop Ebola treatments. For example, NIAID supported Mapp Biopharmaceutical, Inc., in its development of a monoclonal antibody “cocktail” called MB-003, which prevents Ebola virus infection in mice and non-human primates when administered as post-exposure prophylaxis within one to two days of Ebola virus infection. Additionally, NIAID currently is funding development of an optimized anti-Ebola monoclonal antibody product, zMapp, which has superior efficacy compared to earlier cocktails. The zMapp, which is partially derived from MB-003, is a cocktail of three antibodies against Ebola.
In addition, NIAID is funding BioCryst Pharmaceuticals to develop and test BCX4430, a novel nucleoside with broad spectrum antiviral activity including against Ebola virus. To date, BCX4430 has shown efficacy in animal infection models for Ebola and Marburg viruses. A Phase I trial is expected to begin in late 2014 or early 2015. NIAID also is supporting other monoclonal antibody-based broadly-protective filovirus immunotherapeutics.
NIAID is also supporting the development of improved diagnostics for Ebola virus infection. For example, NIAID is funding a Lassa fever recombinant antigen diagnostic. A similar diagnostic is being designed to detect Ebola virus infection. NIAID also is supporting development of multiplex diagnostics, microfluidics-based diagnostics, and optofluidic-based diagnostics for Ebola.
Last Updated January 15, 2015