NIAID is supporting the development of multiple Ebola vaccine candidates that are in various stages of development.
NIAID/GSK Investigational Ebola Vaccine (cAd3-EBOZ)
The NIAID Vaccine Research Center (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, or cAd3-EBOZ, 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 Ebola virus gene inserts but does not replicate further. The gene inserts express an Ebola virus 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 began Phase 2 testing in February 2015 through the launch of the PREVAIL I trial (Partnership for Research on Ebola Virus in Liberia). The randomized, placebo-controlled clinical trial enrolled 1,500 participants. It was originally designed to advance to a Phase 3 trial among 28,000 volunteers but was scaled back because the decline in new Ebola cases made it impossible to conduct the larger study. Findings presented in February 2016 indicate the vaccine was well-tolerated and induced an immune response.
rVSV-ZEBOV Investigational Ebola Vaccine
NIAID has also been involved in testing the rVSV-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 insert. 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, rVSV-ZEBOV proved to be safe and elicited robust antibody responses in all 40 of the healthy adults who received it. The investigational vaccine is now undergoing Phase 2 testing with the cAd3-EBOZ candidate in the PREVAIL I trial in Liberia. Findings of the Phase 2 trial presented in February 2016 indicate the vaccine was well-tolerated and induced an immune response among participants. Additional organizations are testing rVSV-ZEBOV in late-stage clinical trials in West Africa. The Centers for Disease Control and Prevention and the U.S. Department of Health and Human Services(HHS) Office of the Assistant Secretary for Preparedness and Response, in partnership with the Sierra Leone College of Medicine and Allied Health Sciences and the Sierra Leone Ministry of Health and Sanitation launched in April 2015 a combined Phase 2 and 3 trial in Sierra Leone to test the safety and efficacy of rVSV-ZEBOV.
Other Ebola Vaccine Candidates
NIAID and other funding partners supported the development and preclinical and clinical testing of an investigational vaccine regimen designed to specifically protect against the Ebola virus strains responsible for the recent outbreak in West Africa. The vaccine candidate combines the Ad26.ZEBOV vector (based on the AdVac platform developed by Crucell Holland B.V., one of the Janssen Pharmaceutical Companies of Johnson & Johnson) with a modified vaccinia virus Ankara (MVA)-vectored vaccine (MVA-BN Filo) developed by Bavarian Nordic. Crucell and NIAID have supported Phase 1 trials of the vaccine in the United Kingdom and the United States, respectively. Additional Phase 1 trials are underway in Africa, and in July 2015, Crucell initiated a Phase 2 clinical trial of the investigational vaccine in the United Kingdom and France. In October 2015, Crucell launched a clinical trial in Sierra Leone to test the safety and immunogenicity of the regimen. The HHS Biomedical Advanced Research and Development Authority (BARDA) is supporting advanced development of this regimen.
NIAID is also supporting the development of multivalent filovirus vaccine regimens combining non-replicating human adenovirus vectors Ad26 with non-replicating Ad35 (both in development at Crucell Holland B.V.), or Ad26 vectors with Bavarian Nordic’s MVA-BN Filo.
Additionally, NIAID is funding Profectus Biosciences, Inc., to develop additional recombinant vesicular stomatitis virus (VSV)-vectored vaccines against Ebola and Marburg viruses. NIAID is supporting the preclinical studies for the trivalent vaccine against Marburg and the Zaire and Sudan strains of Ebola. The U.S. Department of Defense plans to support an upcoming Phase 1 clinical trial of the monovalent vaccine against the Zaire strain of Ebola. NIAID also is supporting testing of a candidate nanoparticle Ebola vaccine developed by Novavax. When combined with an adjuvant manufactured by Novavax, the investigational vaccine showed promise in nonhuman primates. Initial results from a Phase 1 trial found the vaccine candidate to be well-tolerated and elicited an immune response.
NIAID also is partnering with the University of Texas Medical Branch at Galveston to advance a human parainfluenza virus type 3-vectored Ebola vaccine developed by NIAID scientists. The parainfluenza virus is used as a weakened, replicating viral vector, or carrier, to deliver Ebola genetic material designed to stimulate a protective immune response against Ebola virus. The vaccine candidate is designed to be delivered to the respiratory tract as an aerosol or liquid and induced a robust immune response in monkeys and protected monkeys exposed to Zaire Ebolavirus. NIAID initiated a Phase 1 clinical trial to test the safety and efficacy of the aerosolized version in September 2015.
NIAID is supporting and conducting research to produce a vaccine candidate based on an existing rabies vaccine that would protect against Ebola, Marburg, and rabies viruses. NIAID intramural scientists are working with Thomas Jefferson University investigators to pursue a version of the vaccine for human and veterinary use, as well as a version for African wildlife. The National Institutes of Health licensed the candidate rabies/Ebola vaccines to Exxell BIO, which aims to advance the products through clinical testing and potential commercialization.