Healthy Adult Immune Responses to Vaccine
Conditions
Keywords
Immunity, Ebola Virus, Ebola Hemorrhagic Fever, Healthy, Filovirus
Brief summary
Background: \- Ebola virus is a rare disease that starts with fever and muscle aches, but can lead to death. The 2014 Ebola outbreak in West Africa is the largest to date. There are no approved treatments for Ebola. Researchers want to see if two new vaccines VRC-EBOMVA079-00-VP (MVA-EbolaZ) and VRC-EBOADC069-00VP ( cAd3-EBO ) are safe and able to induce an immune response against Ebola. Objectives: \- To see if the two new vaccines are safe and if they cause any side effects. Also, to study immune responses to the vaccines. Eligibility: \- Healthy adults ages 18-66 Design: * Participants will get one or two study vaccine injections depending on the study group they are assigned to. Each injection will repeat the same schedule: * A needle and syringe will inject the vaccine into an upper arm muscle. * 1-2 days later, participants must call the clinic to report how they feel. * For 7 days they will check their temperature with a thermometer given to them. They will look at the injection site, and measure any redness or swelling with a ruler. They will write down any symptoms they have. * In the first 2 months, participants will have at least 6 clinic visits and 1 phone contact. At each visit, participants will be checked for health changes or problems. They will tell how they feel and if they have taken any medications. Blood and urine samples may be collected. * Participants might need to have extra clinic visits and laboratory tests if they have health changes that need to be checked.
Detailed description
This Phase 1/1b study will examine dose, safety, tolerability and immunogenicity of an investigational MVA-vectored Ebola vaccine in healthy adults. The vaccine encodes wild type (WT) glycoprotein (GP) from Zaire strain of Ebola and will be administered intramuscularly (IM) with needle and syringe. The safety and tolerability of the MVA-EbolaZ will be evaluated at escalating doses of 1x10(7) and 1x10(8) plaque forming units (PFU). Part 1 includes enrollment of vaccine-naive subjects to conduct a dose escalation of the MVA-EbolaZ vaccine and to evaluate the vaccine as a boost for the cAd3-EBO vaccine. In Part 2 of the study, up to 140 subjects who received the cAd3-EBO or cAd3-EBOZ vaccine in VRC 207 study will be boosted with MVA-EbolaZ. The hypotheses are that the study vaccines will be safe and elicit immune responses to Ebola GP, and that the prime-boost regimens will be safe and result in a more polyfunctional response to Ebola GP that is of greater magnitude and duration than response to either of the vaccines alone.
Interventions
BIOLOGICALVRC-EBOMVA079-00-VP (MVA-EbolaZ)
Ebola Modified Vaccinia Virus Ankara Vaccine
BIOLOGICALVRC-EBOADC069-00-VP (cAd3-EBO)
Ebola Chimpanzee Adenovirus Vector Vaccine
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 66 Years
Healthy volunteers
Yes
Inclusion criteria
* INCLUSION CRITERIA: Inclusion Criteria for Groups 1, 2, and 3. A volunteer must meet all of the following criteria to be eligible: 1. 18 to 50 years old. 2. Available for clinical follow-up through the last study visit. 3. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process. 4. Able and willing to complete the informed consent process. 5. Willing to donate blood for sample storage to be used for future research. 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) less than or equal to 40 within the 56 days prior to enrollment. Laboratory Criteria within 56 days prior to enrollment: 8. Hemoglobin within institutional normal range or accompanied by the Principal Investigator (PI) or designee approval. 9. White blood cells (WBC) = 3,300-12,000 cells/mm(3). 10. WBC differential either within institutional normal range or accompanied by the PI or designee approval. 11. Total lymphocyte count greater than or equal to 800 cells/mm(3). 12. Platelets = 125,000-400,000/mm(3). 13. Alanine aminotransferase (ALT) less than or equal to 1.25 times upper limit of normal. 14. Serum creatinine less than or equal to 1.1 times upper limit of normal. 15. Partial thromboplastin time (PTT) less than or equal to 1.1 times upper limit of normal or accompanied by the Principal Investigator (PI) or designee approval. 16. Prothrombin time (PT) less than or equal to1.1 times upper limit of normal or accompanied by the Principal Investigator (PI) or designee approval. 17. HIV-uninfected as evidenced by a negative FDA-approved HIV diagnostic blood test. -Female-Specific Criteria: 18. Negative beta-HCG (human chorionic gonadotropin) pregnancy test (urine or serum) on day of enrollment if woman is presumed to be of reproductive potential. 19. Agrees to use an effective means of birth control from at least 21 days prior to enrollment through 24 weeks after last study vaccination if presumed to be of reproductive potential.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Local and systemic reactogenicity signs and symptoms. | Daily for 7 days following the vaccination |
| Occurrence of adverse events of all severities. | Through 4 weeks after each injection |
| Occurrence of serious adverse events and new chronic medical conditions. | Through 48 weeks after last injection |
Secondary
| Measure | Time frame |
|---|---|
| Antibody responses as measured by ELISA and neutralization assays. | 4 weeks after vaccination. |
| T cell responses as measured by intracellular cytokine staining (ICS)assay. | 4 weeks after vaccination. |
Countries
United States
Outcome results
None listed