cAd3-Marburg Vaccine in Healthy Adults

It is anticipated that about 100 volunteers will be screened in order to enroll a total of 40
participants. The 40 enrolled participants will be evenly split, with 20 in each of the two
dosage groups for cAd3-Marburg. The dose escalation plan includes daily review of any new
safety data by a study clinician, regular review of safety data by the protocol team and a
staged enrollment plan with required interim safety reviews. The study will begin with
enrollment of 3 participants into Group 1 at a rate of 1 participant per day. After at least
7 days of follow-up for the first 3 vaccinated participants, an interim safety review will
occur before enrollment of additional participants into the group. If no safety issues are
identified, an additional 17 participants will be enrolled to complete Group 1. When there is
a minimum of seven days of follow-up safety data from the last enrolled participant in Group
1, an interim safety review will occur. Once no safety issues are identified, enrollment of
participants into the next dose level will begin with the enrollment of 3 participants at a
rate of 1 participant per day. After at least 7 days of follow-up for the first 3 vaccinated
participants in Group 2, an interim safety review will occur before the enrollment of
additional participants into Group 2. If no safety issues are identified, an additional 17
participants will be enrolled to complete Group 2.

Inclusion Criteria:

1. 18 to 50 years old

2. Available for clinical follow-up through Week 48 after enrollment

3. Able to provide proof of identity to the satisfaction of the study clinician
completing the enrollment process. Proof of identity includes a valid U.S.
government-issued or state-issued photo ID such as a driver's license, military ID, or
U.S. passport.

4. Able and willing to provide a personal mobile phone number or home phone number at
which the participant can be reliably contacted. Participants will be contacted
primarily for study visit 2A (Appendix 1), as a reminder of an upcoming visit, and
after missed visits for rescheduling purposes.

5. Able and willing to complete the informed consent process and demonstrate
understanding with a passing score (90% or greater) on the Assessment of Understanding
(AOU) by the third attempt.

6. In good general health without clinically significant medical history.

7. Physical examination and laboratory results without clinically significant findings
and a body mass index (BMI) ≤ 40 within the 56 days prior to enrollment.

Laboratory Criteria within 56 days prior to enrollment:

8. Hemoglobin ≥ 11.5 g/dL for women; ≥13.0 g/dL for men.

9. White blood cells (WBC) = 3,300-12,000 cells/mm3.

10. Total lymphocyte count ≥ 800 cells/mm3.

11. Platelets = 125,000 - 400,000/mm3.

12. Alanine aminotransferase (ALT) ≤ 1.25 x upper limit of normal.

13. Serum creatinine ≤ 1 x upper limit of normal.

14. HIV-uninfected as evidenced by a negative FDA-approved HIV diagnostic blood test.

Female-Specific Criteria:

15. Negative β-HCG (human chorionic gonadotropin) pregnancy test; serum β-HCG at screening
(or urine if screening is the same day as enrollment) and urine β-HCG at enrollment if
woman is of reproductive potential.

16. Agrees to use an effective means of birth control from at least 21 days prior to
enrollment through 24 weeks after study vaccination if assessed to be of reproductive
potential.

Exclusion Criteria:

Volunteer has received any of the following substances:

1. Investigational Ebola or Marburg vaccine in a prior clinical trial or prior receipt of
a cAd3 adenoviral vectored investigational vaccine.

2. Immunosuppressive medications within 2 weeks prior to enrollment.

3. Blood products within 112 days (16 weeks) prior to enrollment.

4. Investigational research agents within 28 days (4 weeks) prior to enrollment.

5. Live attenuated vaccines within 28 days (4 weeks) prior to enrollment.

6. Subunit or killed vaccines within 14 days (2 weeks) prior to enrollment.

7. Current anti-tuberculosis prophylaxis or therapy.

Female-specific criteria:

8. Woman who is pregnant, breast-feeding or planning to become pregnant during the first
24 weeks after study vaccine administration.

Volunteer has a history of any of the following clinically significant conditions:

9. Serious adverse reactions to vaccines such as anaphylaxis, urticaria (hives),
respiratory difficulty, angioedema, or abdominal pain.

10. Allergic reaction to excipients in the study vaccine including gentamycin, neomycin or
streptomycin.

11. Clinically significant autoimmune disease or immunodeficiency.

12. Asthma that is not well controlled.

13. Positive syphilis serology. False-positive results will also exclude a participant.

14. Diabetes mellitus (type I or II).

15. Thyroid disease that is not well controlled.

16. A history of hereditary angioedema (HAE), acquired angioedema (AAE), or idiopathic
forms of angioedema.

17. Idiopathic urticaria within the last 1 year.

18. Hypertension that is not well controlled.

19. Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or
platelet disorder requiring special precautions) or significant bruising or bleeding
difficulties with IM injections or blood draws.

20. A malignancy that is active, currently being treated, or not surgically cured.

21. Seizure in the past 3 years or treatment for seizure disorder in the past 3 years.

22. Asplenia or functional asplenia.

23. Psychiatric condition that precludes compliance with the protocol; past or present
psychoses; or within five years prior to enrollment, history of a suicide plan or
attempt.

24. Any medical, psychiatric, social condition, occupational reason or other
responsibility that, in the judgment of the investigator, is a contraindication to
protocol participation or impairs a volunteer's ability to give informed consent.