Read and report vaccine reactions, harassment and failures.
The first Ebola virus vaccine, ERVEBO, was initially developed in Canada by scientists from the Public Health Agency of Canada’s National Microbiology Laboratory. The vaccine was made by modifying an attenuated strain of a vesicular stomatitis virus (VSV) to permit the expression of an Ebola protein. The license for the vaccine was first held by NewLink Genetics, a U.S. company that was eventually absorbed into Lumos Pharma.
When an Ebola outbreak emerged in Western Africa in early 2014, Canada offered its experimental vaccine to the World Health Organization (WHO). The organization, however, declined this vaccine, as well as one that was under development by GlaxoSmithKline (GSK). A few days after the WHO declared the Ebola outbreak a global health emergency, the Canadian government announced that it would be donating the experimental vaccine to the agency.
The vaccine, however, had never been tested in clinical trials, and while drug companies have an extensive history of using experimental products on persons living in developing countries, WHO decided that clinical trials would be necessary. NewLink Genetics had never conducted large-scale clinical trials and as a result, WHO and other world leaders pushed for the company to partner with or sell the vaccine rights to a larger pharmaceutical company. In late 2014, Merck pharmaceuticals bought the Ebola vaccine rights for $50 million.
The experimental vaccine, which targeted the Zaire ebolavirus, was evaluated in Guinea during the 2014-2016 Ebola outbreak in West Africa. The Phase 3 trial was an open-label, cluster-randomized, controlled ring vaccination trial where clusters of contacts of persons who were confirmed to have Ebola virus and contacts of those contacts were offered immediate vaccination or delayed vaccination (a vaccine after a 21 days).The main outcome of interest was the number of laboratory-confirmed Ebola virus cases occurring at 10 or more days following randomization. This 10-day period was chosen to account for the Ebola virus incubation period and the unknown time frame from vaccination to the development of vaccine-acquired immunity.
The analysis of the randomized clusters in the initial study found that among the 2,108 individuals who immediately received the vaccine, no cases of Ebola virus disease occurred 10 or more days after randomization. However, 10 of 1,429 participants in the delayed group developed Ebola virus disease after randomization. The vaccine was reported to have an efficacy of 100 percent in persons in the immediate vaccination group.
These findings, however, were questioned by independent researchers who stated the following:
“This perfect vaccine efficacy could be true if the two groups had been comparable in all variables but the vaccination. However, the protocol of this cluster-randomised trial reveals a bias with respect to the intervention. After randomisation, people in both types of clusters (immediate and delayed vaccination) were visited by a medical study team and a surveillance team, but the medical study team did not stay in the communities of the delayed vaccination (control) clusters. People in the control clusters were only visited by the medical study team on day 0 to identify controls and obtain informed consent and then on day 21 to vaccinate the controls. By contrast, for the immediately vaccinated clusters, the medical study teams stayed in the communities to follow up the vaccinated participants with active and passive detection of side-effects. The presence or absence of a medical team attending study participants in an African community will have an effect on outcomes. Continuous interaction with the doctors and nurses of the study team for 3 weeks would have affected the knowledge and behaviour (eg, awareness of disease symptoms, keeping distance, general rules of hygiene) of the participants, which in turn would have affected disease transmission. Such changes in knowledge and behaviour are especially important when the basic reproduction number of transmission is very low, as is the case with the Ebola virus. Thus, zero cases in the immediately vaccinated clusters of this unblinded study might have been the result of other factors than the vaccine, and vaccine efficacy might have been lower than 100%. All possible cases of Ebola virus disease might have been averted by behavioural change; in such case, the vaccine efficacy would have been 0%.”
The researchers also warned that inaccurate vaccine efficacy data might have serious and potentially fatal consequences if vaccinated individuals did not follow stringent infection control measures because they assumed complete protection from vaccination.
Adverse events reported during clinical trials of ERVEBO included: injection site pain, swelling, and redness; headache; fever; nausea; fatigue; muscle pain; joint pain, swelling, stiffness, warmth, and redness; abnormal sweating; rash; mouth ulcers; vesicular lesions; arthralgia; arthritis; anaphylaxis; cerebrovascular accident (a type of stroke); hemorrhagic stroke; subarachnoid hemorrhage; pulmonary embolism; and death.
Arthralgia and severe arthralgia were reported at higher rates in persons vaccinated with ERVEBO in comparison to placebo recipients. In some cases, vaccinated individuals experienced persistent and recurrent joint pain. In studies, all joint types were noted to be affected. Persons with a past history of arthritis and females were found to be at a higher risk of arthritis post-vaccination.
The vaccine received full approval for use by the European Commission in November 2019 after the European Medicines Agency (EMA) recommended its use. One month later, on December 19, 2021, Merck’s ERVEBO Ebola virus vaccine received FDA approval for use in persons 18 years of age and older. This vaccine targets Ebola virus disease (EVD), caused by Zaire ebolavirus, and is administered as a single dose.
On February 26, 2020, the CDC’s Advisory Committee on Immunization Practices (ACIP) voted to recommend pre-exposure vaccination of ERVEBO in adults 18 years of age and older who are considered at highest risk of developing Ebola virus disease. These populations include individuals responding to an outbreak of Ebola virus disease, health care personnel working at a federal facility designed to treat persons with Ebola virus diseases, and persons working at a biosafety level 4 facility where Ebola virus is present. ACIP expanded its recommendation for use of the vaccine in 2021 to include healthcare workers providing care at specialized pathogen treatment centers and laboratory and support staff working at Laboratory Response Network facilities.