Safety and immunogenicity trial of Ebola vaccines shows promising results

Ebola outbreaks occur periodically in various countries in sub-Saharan Africa. Although vaccines exist and have already received WHO prequalification once morest Ebola virus from Zaire species, it is essential to continue and intensify efforts to complete the available data in order to develop safe and effective vaccination strategies once morest Ebola in adults and children. The international PREVAC consortium (see box), which includes scientists from Inserm and institutions in Africa, the United States and the United Kingdom, has published the results of a large-scale randomized clinical trial in Africa of the West in the New England Journal of Medicine. These results confirm the safety of three different vaccine regimens and suggest that an immune response is induced and maintained for up to 12 months.

In a context where many countries in sub-Saharan Africa are regularly confronted with Ebola epidemics, vaccines are considered a central tool in combating the spread of the disease. Since 2019, two vaccines have obtained WHO Prequalification once morest Ebola virus from Zaire species: the vaccine rVSVΔG-ZEBOV-GP developed by Merck, Sharpe & Dohme, Corp., and the Advertisement26.ZEBOV et MVA-BN-Filo Johnson & Johnson vaccine regimen.

Beyond these advances, research into Ebola vaccines must continue. Indeed, additional data are needed in order to establish the most appropriate recommendations for the use of these vaccines in different categories of the population.

Three vaccine regimens tested

This is the objective of the international PREVAC consortium. Starting in 2017, a large, multicenter, randomized, placebo-controlled phase 2 trial involved African, European, and American research teams working together in Liberia, Guinea, Sierra Leone, and Mali. This is one of the largest Ebola vaccination trials to date – conducted in adults and children aged one year and older.

The trial aimed to measure the speed, intensity and durability of immune responses generated by three different treatment regimens once morest Ebola, involving the vaccines mentioned above. It also assessed the safety and tolerance of the various products administered.

• The first vaccine regimen tested consisted of injecting a dose of Advertisement26.ZEBOV followed 56 days later with a dose of MVA-BN-Filo.
• The second regimen consisted of injecting a dose of rVSVΔG-ZEBOV-GP.
• Finally, the third diet started with a dose of rVSVΔG-ZEBOV-GP follow-up 56 days later with the same vaccine as a booster.

In total, the trial included 1400 adults and 1401 children aged 1 to 17, who were randomized into several groups to test and compare the three treatment regimens once morest placebo.

The data obtained suggest that the three diets are safe and well tolerated in adults and children. After vaccination and within 7 days following, the majority of participants reported pain at the injection site and other minor symptoms (fever, muscle and joint pain, headache, etc.), which usually disappeared following 7 days.

The three regimens also generated a rapid increase, following 14 days, in the amount of antibodies directed once morest the virus, with a peak between 1 and 3 months following the first vaccination. While it is not yet possible to say whether this immune response prevents infection, current scientific literature suggests a strong correlation between the quantity of these antibodies and the level of protection once morest the virus. These antibodies were detected up to 12 months following the first injection.

“The data collected during this clinical trial is valuable because it confirms the safety and potential efficacy of the available vaccines, making it possible to refine the vaccination recommendations during the two Ebola virus from Zaire epidemic and inter-epidemic periods, in populations at risk”, explains the principal investigator of the lawsuit, Yazdan Yazdanpanah.

“This trial is marked by a high participant retention rate thanks to the unfailing involvement of all professionals in the field, and the support of the population for the research that led to these results”, explains lead researcher Mark Kieh.

“The PREVAC trial is a true success story for international research on emerging and re-emerging infections. We are showing that with strong collaboration built on strong partnerships, we can advance Ebola research in the areas of the world most affected by the disease,” souligne H Clifford Lane, NIAID Deputy Director for Clinical Research and Special Projects.

The work of the PREVAC consortium in West Africa continues, partly thanks to European funding from EDCTP supported by the European Union. Participants will be followed over a period of 5 years to assess the long-term safety of the vaccines and the durability of the immune response. It is crucial to obtain such data, which will shed light, for example, on whether or not it is necessary to provide a vaccination booster to people who have already been vaccinated.