A Safety and Immunogenicity Study of Heterologous and Homologous Prime-Boost Ebola Vaccine Regimens in Healthy Participants

This study consists of 3 parts: the first and third part with standard doses and the second
part with higher doses. All parts are randomized, placebo-controlled, observer-blind to
evaluate the safety, tolerability and immunogenicity of MVA-BN-Filo and Ad26.ZEBOV
administered in different doses, sequences and schedules to healthy adult participants. The
study consists of a screening period of up to 28 days, a vaccination period in which
participants will be vaccinated at baseline (Day 1) followed by a boost on Day 15, 29, or
57, and third vaccine 1-year post-prime (3rd vaccination is optional for subjects in groups
1-8). The total duration of the study will be about 1 year for participants who wiil receive
boost vaccine and about 3 months for participants who will receive placebo and 2 year for
participants who will receive a 3rd dose. Safety will be monitored during the study.

Inclusion Criteria:

- Must be healthy on the basis of physical examination, medical history, and the
investigator's clinical judgment

- Have a body mass index (BMI) ≥18.5 and <35.0 kg/m2

- Women of childbearing potential must have a negative serum β-human chorionic
gonadotropin pregnancy test at screening, a negative urine pregnancy test immediately
prior to each study vaccine administration, and practice adequate birth control
measures from 28 days before the prime vaccination until at least 3 months after the
boost vaccination as specified in the study protocol. If not heterosexually active at
screening, must agree to practice adequate birth control measures if they become
heterosexually active during their participation in the study (from screening onwards
until at least 3 months after the boost vaccination). Agree not to donate eggs (ova,
oocytes) for the purposes of assisted reproduction during participation in the study
(from screening onwards until at least 3 months after the boost vaccination)

- Women of non-childbearing potential, defined as postmenopausal (>45 years of age with
amenorrhea for ≥2 years or any age with amenorrhea for ≥6 months and serum
follicle-stimulating hormone [FSH] >40 mIU/mL) or surgically sterile (hysterectomy,
bilateral tubal ligation, or bilateral oophorectomy), are not required to use the
birth control methods as specified in the study protocol

- A man who has not had a vasectomy and is sexually active with a woman of childbearing
potential must agree to use a double-barrier method of birth control, such as either
condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap
(diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
In case the female partner is using an adequate method of birth control, a
single-barrier method of birth control for the male subject is acceptable. Men must
also agree not to donate sperm during their participation in the study (from
screening onwards until at least 3 months after the boost vaccination)

- Must be available and willing to participate for the duration of the study visits and
follow-up, provide verifiable identification, and have a means to be contacted

Exclusion Criteria:

- Has been vaccinated with a candidate Ebola vaccine

- Has been diagnosed with Ebola disease or exposed to Ebola including travel to West
Africa in the last 12 months. West Africa includes but is not limited to the
countries of Guinea, Liberia, Mali, and Sierra Leone. Participants who anticipate
traveling to epidemic Ebola areas before the start of the long-term follow-up period
will also be excluded from enrollment into the study

- Has received any Ad26- or MVA-based candidate vaccine in the past

- Known allergy or history of anaphylaxis or other serious adverse reactions to
vaccines or vaccine products (including any of the constituents of the study
vaccines), including known allergy to egg or aminoglycosides

- A woman who is pregnant or breast-feeding, or planning to become pregnant while
enrolled in the study or within 3 months after the boost vaccination

- History of diabetes mellitus type 1 or type 2, including cases controlled with diet
alone; thyroidectomy, or thyroid disease requiring medication during the last 12
months; uncontrolled hypertension as defined in the study protocol; or, major
psychiatric illness and/or substance abuse problems during the past 12 months that in
the opinion of the investigator would preclude participation