By Steven Muti
Ebola is a highly contagious and life-threatening disease with a sharp death toll: outbreaks have a documented mortality of up to 90%. Signs of infection appear between 2 and 21 days after initial exposure to the virus, starting with flu-like symptoms but progressing to organ failure, severe systemic bleeding, and septic shock. Without the proper magnitude of immune responsiveness, a majority of patients die within 6 to 16 days of symptom onset. Due to the urgent need of improved and scalable methods for combating the disease and supporting recovery, recent research has focused on understanding the immune response to the ebola virus and developing better treatments including more reliable vaccines.
Fatal cases are distinguished by an over-reactive immune response to the virus known as a “cytokine storm,” during which excessive quantities of pro-inflammatory and immune-stimulating signaling molecules are released into the bloodstream. This causes dormant immune cells positioned throughout the body to simultaneously become activated and weaponized, leading to extensive organ damage and causing internal bleeding. The destruction of multiple cell types, including those involved in the normal blood clotting process, contributes to hemorrhaging and ultimately leads the body out of equilibrium, resulting in fatality.
Scientists developing improved Ebola vaccines have focused on manipulating a key ingredient known as an “adjuvant,” which serves to magnify the immune response to components of the infectious agent contained within the vaccine. By employing the immune signaling molecule Interleukin-12 as an adjuvant, researchers have been able to produce remarkable immune responsiveness against the Ebola virus, leading to complete virus neutralization and functionally curing the disease. Among other immune-activating effects, this adjuvant stimulates cells known as macrophages which eliminate disease-causing agents by migrating to, enveloping, and carefully digesting microbes at sites of infection.
Researchers engineered the vaccine to deliver Interleukin-12 in the form of a DNA sequence known as a plasmid which was designed to target one of the two components of the Ebola virus glycoprotein, part of the virus exterior which normally allows the virus to interact with and infect almost any cell in the human body. Their fascinating delivery method, known as in vivo electroporation, involved the application of an electric current directly to live cells within the patient, creating temporary pores that enabled the entry of the engineered plasmids.
The study sought to determine which part of the ebola virus cells would be most responsive to, as well as which method for delivering the plasmids would be most effective. The researchers identified a specific part of the virus that the immune cells recognized best. Furthermore, they determined that the delivery of the vaccine combined with the application of electric current to the skin provided the most clinical benefit while causing the fewest unwanted side effects.
70% of individuals receiving the vaccine were also shown to develop responsiveness against the virus by an important population of immune cells known as T lymphocytes, which contribute to the long-term defense against reinfection. The protective immune response induced by the vaccine, also observed in individuals that have survived Ebola without vaccination, can be measured by assessing the expression levels of key markers in the bloodstream. Individuals with adequate immune responsiveness may be protected against reinfection for up to and in excess of 10 years.
Since the vaccine is stable at temperatures achievable by refrigerators and may function even when stored at room temperature, the delivery of this vaccine West Africa and its stockpiling in rural areas has become a possibility, offering a feasible method for preventing and controlling future Ebola outbreaks.
Tebas P, Kraynyak KA, Patel A, et al. (2019) Intradermal SynCon® Ebola GP DNA Vaccine Is Temperature Stable and Safely Demonstrates Cellular and Humoral Immunogenicity Advantages in Healthy Volunteers. The Journal of Infectious Diseases, 220(3), 400-410. https://academic.oup.com/jid/article-abstract/220/3/400/5395966
Image Attribution: “PHIL scientists PPE Ebola outbreak.” Date: 1995. Description: This 1995 photograph shows scientist with personal protective equipment (PPE) testing samples from animals collected in Zaire for the Ebola virus. Source: Centers for Disease Control and Prevention. https://commons.wikimedia.org/wiki/File:6136_PHIL_scientists_PPE_Ebola_outbreak_1995.jpg