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Safety of and Immune Response to a DNA Vaccine and a Recombinant HIV-1-MVA Vaccine, Separately and in Combination, in Healthy Adults

Phase 1
Completed
Conditions
HIV Infections
Interventions
Biological: EP-1233
Biological: MVA-mBN32
Registration Number
NCT00428337
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary

The purpose of this study is to determine the safety of and immune response to two experimental vaccines, designed for use in combination, for the prevention of HIV infection in healthy adults.

Detailed Description

The worldwide HIV/AIDS epidemic may only be controlled through the development of a safe and effective vaccine that will prevent HIV infection. DNA-based vaccines alone promote a weak immune response but when used as priming immunogens, followed by a recombinant viral vaccine that is a very attenuated vaccinia (smallpox) vaccine presenting the same immunogens as a booster, immunization with such a combination regimen seems to induce much stronger responses. EP-1233 is a DNA-HIV-recombinant vaccine designed to interact with CD4 (helper-inducer) and CD8 (cytotoxic) T lymphocytes (T cells) to prime CD4 and CD8 cells to respond to HIV components. MVA-mBN32 is a HIV-recombinant viral (MVA) vaccine that through other ways of interacting with CD4 and CD8 cells to immunize (boost) with similar HIV immunogens, may result in a stronger immune response.

The purpose of this study is to determine the safety of and immune response to two experimental vaccines for the prevention of HIV infection, individually and in combination, in healthy adults who have not been previously vaccinated against smallpox. Participants will be randomly assigned to one of three groups. All participants will receive injections at Days 0, 28, 84, and 168 of the study. Participants assigned to Group 1 will receive, on Day 0, one injection in each arm of EP-1233 or placebo and the same study product (EP-1233 or the DNA placebo) on Day 28. Thereafter, each Group 1 participant will receive one injection of MVA-mBN32 or placebo on Days 84 and 168. Groups 2 and 3 will not begin enrollment until safety and immunogenicity data from Group 1 have been evaluated. Participants assigned to Group 2 will receive only the DNA vaccine EP-1233 (or placebo) in each arm on all injection days. Participants in Group 3 will not begin enrollment until safety and immunogenicity data from Group 1 have been evaluated. Participants assigned to Group 3 will receive a consistent regimen of MVA-mBN32 (or placebo) on all injection days. Participants will be required to keep a symptom log for 3 days after each injection and attend clinical visits on Day 0, 14, 28, 42, 84, 98, 168, 182, 273, and 364 of the study. At each of the 10 visits, a physical exam, cardiac assessment, and HIV risk reduction and prevention counseling will occur. Blood collection will occur on Days 0, 14, 42, 98, 182, 273, and 364. Urine collection will occur on Days 14, 42, 98, and 182.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
36
Inclusion Criteria
  • Good general health
Exclusion Criteria
  • Previous receipt of smallpox vaccination
  • HIV-infected
  • Hepatitis B surface antigen positive
  • Participation in prior HIV vaccination trial
  • Immunosuppressive medications within 168 days prior to study entry
  • Receipt of blood products within 120 days of study entry
  • Receipt of live attenuated, medically indicated subunit, or killed (inactivated) vaccines within 30 days of study entry
  • Certain abnormal lab values
  • Pregnant or breastfeeding

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
1MVA-mBN32Participants will receive one injection of DNA vaccine EP-1233 or placebo in each shoulder on Days 0 and 28 and one injection of MVA-mBN32 or placebo in each arm on Days 84 and 168
1EP-1233Participants will receive one injection of DNA vaccine EP-1233 or placebo in each shoulder on Days 0 and 28 and one injection of MVA-mBN32 or placebo in each arm on Days 84 and 168
2EP-1233Participants will receive one injection of DNA vaccine EP-1233 or placebo in each shoulder on Days 0, 28, 84, and 168
3MVA-mBN32Participants will receive one injection of MVA-mBN32 or placebo in each arm on Days 0, 28, 84, and 168
Primary Outcome Measures
NameTimeMethod
Safety of vaccination, as measured by number of adverse events, local and systemic reactogenicity signs and symptoms, changes in electrocardiogram (ECG), cardiac troponin I levels, and differences in other safety laboratory measuresThroughout study
Secondary Outcome Measures
NameTimeMethod
HIV-specific intracellular cytokine staining (ICS) assay and/or interferon-gamma ELISA responsesAt 2 weeks following the third and fourth injection
Vaccinia-specific neutralizing binding assays performed on serum samples from participants receiving the MVA vaccineAt 2 weeks following the final vaccination
Self reports on social impact of participation in studyThroughout study

Trial Locations

Locations (3)

Univ. of Rochester HVTN CRS

🇺🇸

Rochester, New York, United States

Vanderbilt Vaccine CRS

🇺🇸

Nashville, Tennessee, United States

San Francisco Vaccine and Prevention CRS

🇺🇸

San Francisco, California, United States

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