This is a randomized, observer-blind, placebo-controlled trial in male and female subjects ≥18 to <50 years of age. Subjects will be healthy adults based on history, physical examination, and baseline clinical laboratory testing.

Approximately 230 eligible subjects will be enrolled into 1 of 13 treatment groups.

Treatments will comprise two IM doses at a 21-day interval (Day 0 and Day 21), in alternate deltoids with the test article assigned (i.e., saline placebo, dose of EBOV GP vaccine with or without Matrix-M adjuvant), in a 0.5mL injection volume.

Inclusion Criteria:

1. Healthy adult male or females, ≥18 years of age, with an upper limitation of <50 years.
2. Willing and able to give informed consent prior to study enrollment,
3. Able to comply with study requirements, and
4. Women of childbearing potential must have a negative urine pregnancy test prior to each vaccination, and will be advised through the Informed Consent process to avoid becoming pregnant over the duration of the study, and must assert that they will employ an effective form of birth control for the duration of the study. Acceptable forms of birth control are: credible history of continuous abstinence from heterosexual activity or prior surgical sterilization, hormonal contraceptives (oral, injectable, implant, patch, ring), barrier contraceptives (condom or diaphragm), and intrauterine device (IUD). Women with an adequately documented history of surgical sterility are exempt from urine pregnancy testing.

Exclusion Criteria:

1. Any ongoing, symptomatic acute or chronic illness requiring medical or surgical care.

   • Asymptomatic conditions or findings (e.g. mild hypertension, dyslipidemia) that are not associated with evidence of end-organ damage are not exclusionary provided that they are being appropriately managed and are clinically stable (i.e., unlikely to result in symptomatic illness within the time-course of this study) in the opinion of the investigator.
   • Note that illnesses or conditions may be exclusionary, even if otherwise stable, due to therapies used to treat them (see exclusion criteria 2, 5, 7, 8, 9).

2. Participation in research involving investigational product (drug/biologic/device) within 45 days before planned date of first vaccination.

3. History of a serious reaction to prior vaccination.

4. Any occupational or other exposure to Ebolaviruses or recovery from past Ebolavirus disease.

5. Received any vaccine in the 4 weeks preceding the study vaccination; or any Ebolavirus vaccine at any time.

6. Any known or suspected immunosuppressive condition, acquired or congenital, as determined by history and/or physical examination.

7. Chronic administration (defined as more than 14 continuous days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the administration of the study vaccine. An immunosuppressive dose of glucocorticoid will be defined as a systemic dose ≥10 mg of prednisone per day or equivalent. The use of topical and nasal glucocorticoids will be permitted. Inhaled glucocorticoids ≥500µg per day of beclamethasone or fluticasone, or 800μg per day of budesonide are exclusionary.

8. Administration of immunoglobulins and/or any blood products within the 3 months preceding the administration of the study vaccine or during the study.

9. Acute disease at the time of enrollment (defined as the presence of a moderate or severe illness with or without fever, or an oral temperature >38.0°C on the planned day of vaccine administration).

10. Known disturbance of coagulation. The use of ≤325mg of aspirin per day as prophylaxis is permitted, but use of other platelet aggregation inhibitors, thrombin inhibitors, factor Xa inhibitors, or warfarin derivatives is exclusionary, regardless of bleeding history, because these imply treatment or prophylaxis of known cardiac or vascular disease.