This study will test the safety of an experimental vaccine developed to protect against
Ebola virus infection and to determine if the vaccine induces an immune response to the
virus. The Ebola virus causes a disease called Ebola hemorrhagic fever. Symptoms begin with
fever and muscle aches and progress to breathing problems, severe bleeding, kidney problems,
and shock. The infection may be mild, but it can also lead to death. The vaccine used in
this study is made from small parts of Ebola genetic material. It cannot cause Ebola
hemorrhagic fever to develop in those who receive it.
Healthy volunteers 18 to 44 years of age may be eligible for this study. Candidates will be
screened with a medical history, physical examination, and laboratory tests, and complete an
"assessment of understanding" questionnaire to show that they understand the study.
Depending on their order of entry into the study, participants are assigned to receive one
of three vaccine doses or placebo. The first group receives the lowest dose (2 milligram) of
vaccine or placebo. If this dose is safe, then the second group receives 4 mg, and if this
dose is safe, the third group receives 8 mg. Injections are given in a muscle in the upper
arm. Participants receive three injections, each 4 weeks apart (on study days 0, 28, and
Participants record their temperature and symptoms in a diary card for 7 days following each
injection. They return to the clinic 2 to 3 days after each injection and then 2 weeks after
each injection until study week 10. Additional follow-up visits are then scheduled at weeks
12, 24, 38, and 52. At each visit, participants provide a blood and urine sample for testing
and have their vital signs, and lymph nodes checked, their weight measured, and their
symptoms reviewed. Additional laboratory tests may be requested between visits.
This is a Phase I, randomized, placebo-controlled, dose-escalation study of an Ebola DNA
plasmid vaccine. The hypothesis is that the vaccine will be safe for human administration
and elicit immune responses to Ebola. Primary objectives are to evaluate the safety and
tolerability of the investigational vaccine and the secondary objective is to evaluate
immune responses. Randomization assignment will be blinded to subjects, clinical
investigators and laboratory investigators.
- INCLUSION CRITERIA:
A volunteer must meet all of the following inclusion criteria:
1. 18 to 44 years old.
2. Available for follow-up for the duration of the study (12 months).
3. Able to provide proof of identity to the acceptance of the study clinician completing
the enrollment process.
4. Completion of an Assessment of Understanding prior to enrollment and verbalize
understanding of all questions answered incorrectly.
5. Able and willing to complete the informed consent process.
6. Willing to receive HIV test results and willing to abide by NIH guidelines for
partner notification of positive HIV results.
7. Willing to donate blood for sample storage.
8. In good general health without clinically significant medical history.
9. Physical examination and laboratory results without clinically significant findings
within the 28 days prior to enrollment.
Laboratory Criteria within 28 days prior to enrollment:
10. Hematocrit equal to 34% for women; 38% for men.
11. Normal fibrinogen levels, D-dimer immunoassay less than 2.0 microg/mL, and RBC
morphology without evidence of microangiopathic hemolysis.
12. WBC count: Non-African Americans: equal to 3,300-12,000 cells/mm3, African-Americans:
equal to 2,500 - 12,000 cells/mm3 (in the absence of clinical or pathological
13. Differential either within institutional normal range or accompanied by site
14. Total lymphocyte count: Non-African Americans: equal to 800 cells/mm3, African
Americans: equal to 650 cells/mm3 (in the absence of clinical or pathological
15. Platelets within institutional normal limits.
16. Prothrombin time and activated partial thromboplastin time (PT, PTT) within
institutional normal range.
17. Alanine aminotransferase (ALT) (also called SGPT) = upper limit of normal range
18. Serum creatinine = upper limit of normal range
19. Negative Food and Drug Administration (FDA)-approved HIV blood test
20. Negative hepatitis B surface antigen (HbsAg)
21. Negative antibody to hepatitis C virus (anti-HCV), or negative HCV PCR if the
anti-HCV is positive.
22. Normal urinalysis defined as negative glucose, negative or trace protein, and
negative hemoglobin by dipstick.
23. Negative pregnancy test (urine or serum) for women presumed to be of reproductive
24. A female participant must meet one of the following criteria:
No reproductive potential because of menopause (one year without menses) or because of a
hysterectomy, bilateral oophorectomy, or tubal ligation,
Participant agrees to be heterosexually inactive at least 21 days prior to enrollment and
throughout the duration of the study,
Participant agrees to consistently practice contraception at least 21 days prior to
enrollment and throughout the duration of the study by one of the following methods:
- condoms, male or female, with or without a spermicide
- diaphragm or cervical cap with spermicide
- intrauterine device
- contraceptive pills or patch, Norplant, Depo-Provera or other FDA-approved
- male partner has previously undergone a vasectomy for which there is documentation
A volunteer will be excluded if one or more of the following conditions apply.
Volunteer has received any of the following substances:
2. Immunosuppressive or cytotoxic medications within the past six months with the
exception of corticosteroid nasal spray for allergic rhinitis or topical
corticosteroids for an acute uncomplicated dermatitis
3. Blood products within 120 days prior to HIV screening.
4. Immunoglobulin within 60 days prior to HIV screening.
5. Live attenuated vaccines within 30 days prior to initial study injection.
6. Investigational research agents within 30 days prior to initial study injection.
7. Medically indicated subunit or killed vaccines, e.g. influenza, pneumococcal, or
allergy treatment with antigen injections, within 14 days prior to initial study
8. Current anti-TB prophylaxis or therapy.
Volunteer has a history of any of the following clinically significant conditions:
9. Serious adverse reactions to vaccines, such as anaphylaxis, hives, respiratory
difficulty, angioedema, or abdominal pain.
10. Autoimmune disease or immunodeficiency.
11. Asthma that is unstable or required emergent care, urgent care, hospitalization or
intubation during the past two years or that requires the use of oral or intravenous
12. Diabetes mellitus (type I or II), with the exception of gestational diabetes.
13. Thyroid disease including history of thyroidectomy and diagnoses that required
medication within the past 12 months.
14. Serious angioedema episodes within the previous 3 years or requiring medication in
the previous two years.
15. Hypertension that is not well controlled by medication or is more than 145/95 at
16. 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.
17. Malignancy that is active or treated malignancy for which there is not reasonable
assurance of sustained cure or malignancy that is likely to recur during the period
of the study.
18. Seizure disorder other than: 1) febrile seizures under the age of two, 2) seizures
secondary to alcohol withdrawal more than 3 years ago, or 3) a singular seizure not
requiring treatment within the last 3 years.
19. Asplenia or any condition resulting in the absence or removal of the spleen.
20. Psychiatric condition that precludes compliance with the protocol; past or present
psychoses; past or present bipolar disorder requiring therapy that has not been well
controlled by medication for the past two years; disorder requiring lithium; or
suicidal ideation occurring within five years prior to enrollment
21. Any medical, psychiatric, or social condition, or occupational or other
responsibility that, in the judgment of the investigator, would interfere with or
serve as a contraindication to protocol adherence or a volunteer's ability to give