Ebola virus disease is caused by an infection with a virus known as the Ebolavirus. The disease is characterized by symptoms such as fever, body aches, diarrhoea, bleeding, and vomiting.

Vaccination is one of the most effective ways to prevent illness caused by viruses. A vaccine contains a non-functional part of the virus that is recognized by the body's protective immune system. The body then produces a response that prevents illness if the person is exposed to that virus again.

The investigational treatment consists of a 2 dose vaccine regimen, 1 dose of Ad26.ZEBOV vaccine, followed by 1 dose of MVA-BN-Filo vaccine, for the prevention of Ebola virus disease (Zaïre ebolavirus species). The regimen has been studied in 14-, 28-, 56- and 84-day intervals in other clinical studies.

In this study, researchers want to know the safety of the Ebola vaccine regimen in different groups or cohorts of participants at 28-, 56-, and 84-day schedules. In addition, researchers want to understand the immune responses induced by the vaccine regimens by performing some tests.

Participants can take part in this study if they have never received an Ebola vaccine, have not been diagnosed with Ebola virus disease, and have not travelled to any place where Ebola virus disease was confirmed up to 1 month before the study starts. Participants in the human immunodeficiency virus (HIV*)-infected cohort should have a documented HIV infection for at least 6 months before study start and taking medicines for the treatment of HIV infection for the duration of the study.

*HIV infection affects cells of the immune system and decreases their ability to fight infections.

During the study, participants will go through screening to confirm if they can take part in the study. Participants will then be divided into 4 groups as shown below.

• Cohort 1: Healthy adult and elderly participants between 18 to 70 years of age
• Cohort 2: Participants with HIV infection between 18 to 50 years of age
• Cohort 2b: Healthy children between 12 to 17 years of age
• Cohort 3: Healthy children between 4 to 11 years of age

Within each Cohort, participants will be further divided into 2 or 3 groups to test the different intervals between the first and the second vaccine.

All participants will receive either study vaccine (Ad26.ZEBOV and MVA-BN-Filo) or placebo, which does not contain the study vaccine, but looks like it. All vaccines will be given as an injection in the muscle. The first dose (Ad26.ZEBOV or placebo) will be given on Day 1 and the second dose (MVA-BN-Filo or placebo) will be given on either Day 29, 57, or 85, depending on which group and cohort the participant is in.

At selected study sites for Cohort 1, a third vaccination with Ad26.ZEBOV (booster dose), will be given at least 1 year after the first dose to participants who are eligible and agree to a booster vaccination. This booster dose will only be studied at 28- and 56-day schedule to assess safety and immune responses induced by the booster dose.

During the study, participants will undergo different study assessments and tests. It includes blood tests, vital signs (such as pulse, blood pressure, and temperature), electrocardiograms, physical exams, pregnancy test for women, and any side effects reported by the participants. Blood samples will be taken at several time points to know how many people responded to the vaccine regimen and to which extent. There will be a follow-up phase until Day 365 to monitor participants’ health. Participants in Cohort 1 who receive the booster vaccination with Ad26.ZEBOV will also be followed up for safety and immune response assessments up to 1 year after the booster vaccination.

The overall duration of the study can be up to 3 to 4 years.

This is a randomized, observer-blind, placebo-controlled, parallelgroup, multicenter, Phase 2 study evaluating the safety, tolerability and immunogenicity of 3 heterologous prime-boost regimens using Ad26.ZEBOV as prime and MVA-BN-Filo as boost vaccination, administered at 28-, 56- and 84-day (Group 1, 2 and 3 as above) intervals, in healthy adults and elderly participants. A 28- and 56-day (Groups 1 and 2, as above) schedule will be evaluated in HIV infected participants and in healthy children in 2 age strata.

The study consists of a screening phase of up to 8 weeks, a vaccination phase in which participants will be vaccinated at baseline (Day 1) followed by a boost vaccination on Day 29, 57 or 85, a postvaccination phase and long-term follow-up phase until Day 365.

Participants in Cohort 1 substudy (Group 1 and 2) who received Ad26.ZEBOV and MVA-BN-Filo (at selected sites) will receive Ad26.ZEBOV as third vaccination and who received placebo will receive placebo as third vaccination (at least 1 year post prime vaccination). All participants within a cohort will be followed in a blinded manner by the site until the last subject in that cohort has completed the study.

This study will be conducted in Africa and the enrollment will take place sequentially in three cohorts: the first cohort will consist of healthy participants (18 - 70 years); the second cohort (2a) will include HIV-infected participants (18 to 50 years) and healthy children 12 to 17 years (cohort 2b); the third cohort will include children aged 4 to 11 years inclusive will be enrolled. Within each cohort, participants will be randomized in a 5:1 ratio to receive active vaccine versus placebo.

Safety evaluations will include assessments of adverse events, an electrocardiogram (ECG) for adult participants at screening, physical examination, vital signs (blood pressure, pulse/heart rate, body temperature), clinical laboratory and pregnancy testing. An independent data monitoring committee (IDMC) will be established to monitor data on a regular basis to ensure the continuing safety of the participants enrolled in the study.