Providing a Ring of Protection
Similar to the method used to eradicate smallpox, a ring vaccination strategy involves tracking the epidemic and recruiting those at heightened risk of infection due to their connection to a patient with the virus.
When a patient’s Ebola infection status is confirmed by a laboratory, the participants in the “ring” are defined as:4
- Individuals who in the last 21 days: lived in the same household, were visited by the patient after development of symptoms, visited the patient, or were in close physical contact with the patient’s body, body fluids, linen, or clothes
- Neighbors, family, or extended family members in the closest geographic boundary of all contacts, plus household members of all high-risk contacts who do not live in the same location as the patient
- Healthcare and frontline workers who may be in contact with Ebola patients
Each ring typically includes an average of 150 people; participation is free and voluntary.4 Each person who consents receives 1 dose of the vaccine. For the outbreak in North Kivu, the National Regulatory Authorities and the Ethics Committee of the Democratic Republic of the Congo approved the inclusion of children aged >1 years.4 Pregnant women were excluded from participation in the vaccination ring.4
The Road to a Licensed Ebola Vaccine
When researching the safety and efficacy of an Ebola vaccine, there are a number of unknowns. These issues include:5
- Sparse data regarding vaccine use in children and pregnant women, as these populations are commonly a part of exclusion criteria in clinical trials
- Sparse data has been generated in high risk, immunocompromised populations, particularly in people with HIV, and the elderly
- Development of fast and long-lasting immune responses to ensure longer term protection
- Understanding the correlation between immune response and clinical protection
- Investigating adverse events due to the vaccine
- Promoting community engagement and building trust throughout the clinical trial process
Clinical trials that can provide useful data in the above areas are crucial to developing a viable, commercially approved Ebola vaccine.
A Trying Time: An Overview of Current Clinical Trials
Several clinical trials are currently underway to research the safety and efficacy of a vaccine for the Ebola virus. As of December 4, 2018, 47 completed trials, 11 active and not recruiting, and 10 recruiting studies are registered on ClinicalTrials.gov. Four studies have posted their results publicly.
In late November 2018, the Ministry of Health of the Democratic Republic of the Congo launched a randomized control, multi-drug trial to evaluate the effectiveness and safety of drugs used in the treatment of Ebola patients. The trial is part of a multi-outbreak, multi-country study under the umbrella of the World Health Organization. The trial is coordinated by the organization, but led and sponsored by Congo’s National Institute for Biomedical Research in partnership with the country’s Ministry of Health, and in conjunction with the National Institute of Allergy and Infectious Diseases, part of the United States’ National Institutes of Health, and the Alliance for International Medical Action, as well as several other organizations.6
In addition, several trials have focused on researching the effectiveness of the rVSV-ZEBOV vaccine, including:5
- The Ebola Ça Suffit vaccination trial in Guinea, an open-label, cluster-randomized trial that evaluated vaccine effectiveness in case contacts, where clusters of contacts of Ebola cases were randomly assigned for immediate or delayed vaccination. Although found to be 100% effective in individuals vaccinated in the immediate group compared with those in delayed group, the extent of the efficacy is under scrutiny.
- The Partnership for Research on Ebola Vaccines in Liberia I’s randomized, double-blind, placebo-controlled trial (PREVAIL I) assessed the rVSV-ZEBOV vaccine and the chimpanzee adenovirus type 3-vectored Ebola virus vaccine (chAd3-EBO-Z) in 1,500 adults. Researchers found that 1 month after vaccination, 71% of people who received chAd3-EBO-Z, and 84% of those who received rVSV-ZEBOV had an immunogenic response to Ebola, compared with 3% of people who received placebo. At 12 months, 64% and 80% of individuals maintained an antibody response after receiving the chAd3-EBO-Z and rVSV-ZEBOV vaccine, respectively.
- Additional data on rVSV-ZEBOV has been captured in the Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE) study, which enrolled more than 8,000 healthcare and frontline workers in Sierra Leone and Guinea. Trial results indicate that the rVSV-ZEBOV vaccine has an acceptable safety profile and induces immunity (demonstrated as 89%-100% antibody response) in adults that lasts at least 24 months.
- A trial for an adenovirus type 26-vectored vaccine encoding Ebola virus glycoprotein (Ad26.ZEBOV) boosted by a modified vaccinia Ankara-vectored vaccine encoding glycoproteins from Ebola, Sudan, and Marburg viruses, as well as the nucleoprotein of Tai Forest virus resulted in seroconversion frequencies of 79%-89% by day 14 after vaccination that was sustained for at least 360 days, and did not result in any serious vaccine-related adverse events, according to researchers.
- The single-dose chAd3-EBO-Z vaccine also has been studied. Boosted with monovalent chimpanzee adenovirus (MVA), the chAd3-EBO-Z vaccine provoked B-cell and T-cell immune responses to ZEBOV that were better than those induced by the chAd3-EBO-Z vaccine alone, and antibody responses remained positive for six months after vaccination.
- The recombinant adenovirus type 5-vectored Ebola vaccine was found safe and immunogenic in different trials, inducing humoral and cellular immune responses in 100% of 84 adult volunteers.
Researchers and other Ebola experts agree that it is important to investigate different vaccination strategies, including contact and post-exposure vaccination, targeted preventive vaccination, and widespread preventive vaccination of high-risk populations such as healthcare workers and those residing in areas of recurrent outbreaks, to effectively respond to future outbreaks. Developing and distributing a safe and efficacious licensed vaccine is the first step toward eradicating Ebola in Congo—and beyond.
- HealthDay. CDC Director Says Congo Ebola Outbreak May Be Uncontainable. MPR. https://www.empr.com/news/congo-ebola-outbreak-is-uncontainable-centers-for-disease-control-and-prevention/article/813070/. Published November 7, 2018. Accessed December 4, 2018.
- U.S. Food and Drug Administration. FDA authorizes emergency use of first Ebola fingerstick test with portable reader. U.S. Food and Drug Administration. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm625502.htm. Published November 9, 2018. Accessed December 4, 2018.
- Vogel G. Testing new Ebola tests. Science. 2014;345(6204):1549-1550. doi:10.1126/science.345.6204.1549.
- World Health Organization. Ebola Frequently Asked Questions. World Health Organization. http://www.who.int/ebola/drc-2018/faq-vaccine/en/. Published October 30, 2018. Accessed December 4, 2018.
- Lévy Y, Lane C, Piot P, et al. Prevention of Ebola virus disease through vaccination: where we are in 2018. The Lancet. 2018;392(10149):787-790. doi:10.1016/s0140-6736(18)31710-0.
- World Health Organization. Democratic Republic of the Congo begins first-ever multi-drug Ebola trial. World Health Organization. http://www.who.int/news-room/detail/26-11-2018-democratic-republic-of-the-congo-begins-first-ever-multi-drug-ebola-trial. Published November 26, 2018. Accessed December 4, 2018.