Measuring the safety, efficacy of a vaccine against Ebola virus disease

The 2014-2015 Ebola epidemic affected several countries in West Africa, leading to the death of more than 11'000 people. Although this epidemic of Ebolavirus disease is over, there is no knowing if, when or where another may strike. It is therefore more important than ever to find a reliable vaccine against this deadly disease. Research on vaccines, which was ongoing during the epidemic in West Africa, is now yielding promising results.

Important progress in understanding the vaccine

In an article published on April 12, 2017, in Science Translational Medicine, a team from the HUG and the UNIGE, working in collaboration with researchers and clinicians in several other countries in Europe and Africa, has defined a formula that measures the reliability and efficacy of vaccines that might help prevent or limit future outbreaks.

The rVSV-ZEBOV vaccine (recombinant vesicular stomatitis virus-vectored Zaire Ebola vaccine) had already been shown to stimulate the immune system in human volunteers; and in a field trial in 2015 it successfully protected people who had been exposed to Ebola patients from contracting the disease themselves. Yet concerns had been raised during the Geneva trial regarding side effects. What the Geneva team has now published is a detailed examination of the blood plasma of 115 healthy volunteers from Geneva, some of whom received either a low-dose or a high dose of vaccine, while others received a placebo vaccine.

When a vaccine enters the bloodstream, dozens of inflammatory markers that are naturally present see their concentrations change over the next few days. The researchers investigated 15 of them (different varieties of chemokines or cytokines). They found that 1-3 days after the vaccine was administered, the concentration of 6 of these 15 markers had measurably increased. Using a statistical procedure known as principal components analysis, the Geneva team succeeded in producing a simple score that makes the activity of the vaccine much easier to monitor. This "signature" contains only 5 of the 6 markers most likely to change in the presence of the rVSV-ZEBOV vaccine: together, they account for over two-thirds (68%) of the variation in blood cytokine/chemokine activity.

The Geneva Signature found in Gabon

The signature was found to be stronger in volunteers who received the higher dose than in those who got the lower dose.

Importantly, the "Geneva signature" was applied to blood samples from a similar trial that took place in Lambaréné, Gabon, where healthy volunteers had also received the rVSV-ZEBOV vaccine. The same markers were elevated and correlated with side effects and later immunity in the same way.

The 5 markers in the signature are: monocyte attractant protein 1 (MCP-1), the interleukin-1 receptor antagonist (IL-1Ra), tumor necrosis factor (TNF-alpha), interleukin-10 and interleukin-6. Several of these are produced by monocytes or are known to interact with them, so the results imply that monocytes play a critical role in the efficacy and safety of the rVSV-ZEBOV vaccine.

In the case of many other vaccines, such as one recently developed against H1N1 influenza, the chemical markers mostly belong to another category of white blood cells: lymphocytes. Taken together, these signatures help understand how vaccines stimulate the immune system in very different ways to tackle various types of virus. This latest discovery therefore opens up encouraging perspectives for investigating the safety, efficacy and mechanisms of other emerging vaccines.