Ebola Virus Disease and Ebola Vaccines
Ebola virus particles budding from African green monkey kidney cells
Ebola virus disease (EVD) emerged at unprecedented epidemic levels in West Africa in 2014. Whereas previous EVD outbreaks were contained fairly quickly, this epidemic spread to crowded urban areas where transmissions continued unabated for many months.
Retrospective analysis indicates that the first case of the disease may have occurred at the end of 2013. An 18-month-old boy in a small village in Guinea became ill and died in late December, and the disease began to spread. It wasn’t until late March 2014 that the disease-causing agent was identified as Ebola virus. Through the fall of 2014, the epidemic was ongoing in Sierra Leone, Guinea, and Liberia. Nigeria and Senegal had small outbreaks related to importations from neighboring countries, but public health authorities there were able to contain spread of the disease. Several cases and deaths were reported from Mali, but spread was limited. In total, by the time the epidemic was over in March 2016, 11,325 confirmed, probable, and suspected deaths occurred. Total EVD cases numbered 28,652.
Transmission of the disease was limited to West African countries, with the exception of several transmissions in healthcare settings in Europe and the United States. Two U.S. nurses and one Spanish nurse became ill from contact with patients who acquired the disease in West Africa. The nurses recovered.
Ebola virus disease has no cure, but supportive care in a hospital setting can increase a patient’s chance for survival. Additionally, plasma transfusions from convalescent patients and an experimental antibody preparation have been used to treat certain patients. It is not possible to say at this time whether these treatments have had an effect on the course of the disease in the patients who received them.
Ebola virus was first identified in 1976. By the end of that year, two related strains of the virus were known–Ebola Zaire and Ebola Sudan. Three other strains are now known to exist. Vaccine development began in the late 1970s: results from a test of inactivated Ebola vaccine in guinea pigs were published in Lancet in 1980. Because EVD outbreaks are rare and have, until 2014, been controlled quickly, commercial vaccine manufacturers have demonstrated little urgency in advancing vaccines through clinical trials. That changed in 2014: several vaccines previously tested only in animals are being fast-tracked into Phase 1 clinical trials.
ClinicalTrials.gov, a global registry of trials involving human subjects, lists several Ebola vaccine trials in progress. Ebola Zaire is the strain of the virus that is responsible for the 2014 outbreak; accordingly, all of the vaccine candidates being advanced are designed to prevent that strain. If these vaccines work for Ebola Zaire, it is very likely that the same principles can be applied to the other strains.
The two front-running vaccine candidates are a GSK chimpanzee adenovirus vector vaccine (including several versions of it) and a Merck/NewLink Genetics recombinant vaccine. Both are being tested in a single Phase 2 trial in Liberia in those at risk for EVD. The trial is being run by NIAID/NIH and began recruiting participants in fall 2015.
The Ebola vaccine licensed by NewLink Genetics in Ames, Iowa, was originally developed by the Public Health Agency of Canada, which still holds intellectual property rights for it. The vector for this monovalent Ebola Zaire vaccine is an attenuated vesicular stomatitis virus — a virus, like rabies virus, in the Rhabdoviridae family. Vesicular stomatitis virus (VSV) can infect humans though this is a self-limited infection. A safe VSV vaccine for animals has been developed for animal use but it is not currently marketed in the United States.
The version of the GSK Ebola vaccine in the Phase 2 trial is monovalent and offers protection from Ebola Zaire only. This vaccine uses an adenovirus to deliver key Ebola antigens to human cells. Adenoviruses can cause a variety of diseases, but attenuated adenoviruses are safe and have been studied as vaccine vectors. A related bivalent (Ebola Zaire and Ebola Sudan) chimpanzee adenovirus vaccine is being tested in a Phase 1 trial at the NIH Clinical Center.
A vaccine candidate originating from Thomas Jefferson University’s Vaccine Center may advance to clinical trials in humans. This vaccine, developed by Jefferson’s Matthias Schnell, delivers Ebola antigens with an inactivated rabies virus vector. Versions of the vaccine, which have also delivered both Ebola Zaire and Ebola Sudan antigens as well as Marburg virus antigens, have been tested in macaques. Funding from the National Institute of Allergy and Infectious Diseases and the Department of Defense allowed production of a clinical lot of the vaccine for a potential Phase 1 trial.
Johnson & Johnson has a prime-boost Ebola vaccine in development. This two-phase strategy starts with direct exposure to DNA (the “prime”) followed by offering the same or similar antigen in a virus that does not replicate well in human tissue (“the boost”). This approach has been shown in a variety of settings to yield a robust immune response to the antigen of interest. The Phase 1 trial starts in January 2015 in the United States and Europe. The first dose of the vaccine uses a DNA vaccine that primes the immune system to make Ebola Zaire and Ebola Sudan surface proteins; the boost vaccine is based on a recombinant adenovirus vector that delivers an Ebola Zaire surface protein.
More Phase 2 and 3 vaccine trials are already being planned. In many cases, trial participants will be those at high risk of contracting the disease, such as healthcare workers and family members of people who have EVD.
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Johnson & Johnson announces major commitment to speed Ebola vaccine development and significantly expand production. Press release. October 22, 2014. Accessed 04/19/2017.
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University of Maryland School of Medicine begins Ebola vaccine trial in Mali. Accessed 04/19/2017.
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Last update 19 April 2017