The goal of this randomized controlled trial is to investigate whether individuals in DRC previously vaccinated with Zabdeno/Mvabea® or Ervebo® vaccine schedules against Ebola virus can be safely and adequately boosted with homologous or heterologous vaccine schedules.

Participants will be randomized to receive either a homologous or heterologous vaccine schedule and will be asked to come to the clinic at prespecified timepoints over a period of 6 months to collect blood samples for comparison of immunological responses against Ebola virus between both schedules. Safety and tolerability of the vaccines will be evaluated by recording Adverse Events (AE's) and grading physical and vital signs evaluations.

The aim of this randomized controlled with four arms is to investigate whether individuals previously vaccinated with Zabdeno/Mvabea® or Ervebo® vaccine schedules against Ebola virus can be safely and adequately boosted with homologous and heterologous vaccine schedules. We hypothesize that heterologous booster vaccine schedules generate a non-inferior boosting in antibodies and cellular responses against Ebola virus as compared to homologous schedules and incite a similar safety profile.

Based on the predefined variables (living place and time since vaccination), the research team will pre-select and re-contact individuals previously included in the Phase III EBOVAC vaccine database, EBOSURV participant database, and the Programme Élargi de Vaccination (PEV) database. Participants will be contacted by phone and, if they agree to participate, they are scheduled on predefined screening/recruitment days taken place at the 2 recruitment sites: INRB Goma and INRB Kinshasa.

A total of 624 participants will be included, 312 will be previously vaccinated with Zabdeno/Mvabea® and 312 participants with Ervebo®. Within those two groups, half of the participants (n=156) will be randomized to a single Ervebo® booster vaccine and the other half (n=156) to a single Zabdeno® booster vaccine. Participants will be asked to come to the clinic at prespecified timepoints over a period of 6 months to collect blood samples for comparison of antibody- and cellular response against EBOV between homologous and heterologous schedules. Safety and tolerability of the vaccines will be evaluated by recording Adverse Events (AE's) and grading physical and vital signs evaluations. An additional 50 non-vaccinated participants will be recruited in Kinshasa for assay optimization.

In case of insufficient participants living close to the recruitment centers, a community outreach will be undertaken with a lower amount of visits for logistical reasons.

Inclusion Criteria:

• Subjects who received either the Ervebo® vaccine (MSD), or the full Zabdeno, Mvabea® vaccine regimen (J&J) more than 4 months prior to recruitment
• Subjects between 18 and 50 years of age at time of randomization
• Subject must be willing and able to provide informed consent
• The subject must be in possession of an identification card (or other identification document)
• Agreement to refrain from blood donation and other vaccinations 30 days after booster vaccination
• Agreement to share and discuss participant's medical history, medical records and concomitant medications when relevant

Exclusion Criteria:

• Participants who previously experienced active Ebola Virus Disease (EVD)
• Receipt of any vaccine (licensed or experimental) within 30 days prior to recruitment
• Receipt of an additional booster dose of either Ervebo®, Zabdeno®, or any experimental Ebola vaccine
• Incorrect or incomplete primary vaccination scheme with the Zabdeno, Mvabea® (J&J) vaccine
• Administration of immunoglobulins and/or any blood products within three months prior to recruitment.
• Fever (>38°C) within last 24 hours prior to recruitment.
• Any confirmed or suspected immunosuppressive or immunodeficient state (incl. cancer and HIV); asplenia; recurrent severe infections and use of immunosuppressant medication within the last 6 months, except topical or short-term oral steroids.
• Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder and neurological illness (mild/moderate well controlled comorbidities are allowed)
• History of anaphylaxis, allergic disease or reactions to any component of the study vaccines
• History of bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venipuncture
• History of any thrombotic disorder, thrombocytopenia, thrombotic thrombocytopenia syndrome (TTP), or heparin-induced thrombocytopenia and thrombosis (HITT)
• Any other significant disease, disorder, planned surgery, or finding which may significantly affect the ability of the volunteer to participate in the study or impair interpretation of the study data
• Suspected or known alcohol or drug dependency
• Subject is not readily available by telephone, email or physical address

The non-vaccinated control group will also adhere to all the above in- and exclusion criteria, with exemption of:

• Agreement to refrain from blood donation and other vaccinations 30 days after study vaccination
• Subjects who received either the Ervebo® vaccine, or the full Zabdeno, Mvabea® vaccine regimen more than 4 months prior to recruitment

The latter is rather introduced as an additional exclusion criteria:

• Subjects who received either the Ervebo® vaccine or the full Zabdeno, Mvabea® vaccine regimen