An international team based at Geneva University Hospitals (HUG) and the University of Geneva (UNIGE) has succeeded in defining a "formula" for how a vaccine stimulates the immune system against the Ebola virus.
Author Geneva University Hospitals
By studying the plasma of 115 volunteers from Geneva who took part in the clinical trial of the rVSV-ZEBOV vaccine candidate, researchers found that knowing the concentration of five inflammation markers was enough to understand the essence of the immune response against the virus.
The "Geneva rVSV-ZEBOV formula", published on Wednesday April 12 in the journal Science Translational Medicine, is a practical, easy-to-use equation: a summation of the concentrations of the five substances in question, whose activity is controlled by monocytes - a class of white blood cells known to do battle with the Ebola virus in the human body. This formula holds great promise for studying the efficacy and safety of new vaccines.
In 2014-2015, the Ebola epidemic affected several countries in West Africa, where it caused more than 11,000 deaths. Although this epidemic is over, there is no way of knowing when and where Ebola will strike again. Vaccine research - already underway at the time of the epidemic - continues and is now delivering important results.
Decisive progress in understanding the vaccine
In an article published on April 12, 2017 in the journal Science Translational Medicine, a team of researchers from the HUG and the UNIGE Faculty of Medicine, working in collaboration with researchers and physicians from several other institutions in Europe and Africa, present a formula for measuring the progress and effectiveness of vaccines administered, making it possible to prevent or limit future epidemics linked to the Ebola virus.
The rVSV-ZEBOV vaccine (recombinant vesicular stomatitis virus-vectored Zaire Ebola vaccine) was already known for its ability to effectively stimulate the immune system. In a field trial in 2015, it had prevented volunteers exposed to Ebola-infected patients from contracting the disease themselves. However, during the clinical trial conducted in Geneva, concerns arose about side effects. This new research focuses on 115 volunteers in Geneva who received a low dose of the vaccine, a higher dose or a placebo. Their blood plasma was analyzed in detail.
In the days following the administration of a vaccine, the concentration of dozens of inflammation markers present in the blood can change. The researchers analyzed 15 of these substances (mainly chemokines and cytokines). They found that, one to three days after vaccination, the concentration of these substances increased markedly, proving the vaccine's action. Using a statistical method called Principal Component Analysis (PCA), they were able to reduce the number of substances to be measured, making it easier to track vaccine-induced activity in the body. This formula or "signature" contains just five markers, which explain more than two-thirds (68%) of the variation in cytokine and chemokine concentration.
A Geneva "signature" found in Gabon
The formula gives a higher result for inflammation markers in volunteers who received a higher dose of vaccine than in those who received the lower dose.
The "Geneva Signature" was also applied to blood samples from Lambaréné (Gabon), as part of another clinical trial using the rVSV-ZEBOV vaccine; the same markers were elevated, and showed an identical correlation with side effects and immune activity.
In detail, the five markers making up the formula are monocyte-attracting protein 1 (MCP-1), interleukin-1 receptor antagonist (IL-1Ra), tumor necrosis factor (TNF-alpha), and interleukins 6 and 10. Several of these factors are produced by or interact with monocytes, confirming that this type of white blood cell does indeed play a key role in the action of the rVSV-ZEBOV vaccine.
Other vaccines act by stimulating different categories of white blood cells: for example, the vaccine targeting the H1N1 flu virus acts on lymphocytes. These signatures help us to understand how vaccines stimulate the immune system, and open up new avenues for studying the safety, efficacy and mechanisms of action of future vaccines.