Immune Response to an HIV DNA Plasmid Vaccine Prime Followed by Adenovirus Boost in HIV-uninfected Individuals
The purpose of the study is to determine the safety of mucosal immune responses to a DNA HIV vaccine followed by an adenoviral vector HIV vaccine in HIV uninfected adults.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||A Phase 1b Clinical Trial to Evaluate Mucosal Immune Responses to a DNA Plasmid Vaccine Prime Followed by an HIV-1 Adenoviral Vector Boost in Healthy Adenovirus Type 5 Seronegative HIV-1-uninfected Adults|
- HIV-specific T-cell response rates detected in specimens collected from the rectum, semen, or cervix as assessed by IFN-γ ELISpot assay and/or flow cytometry [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Local and systemic reactogenicity signs and symptoms, adverse events and severe adverse events. [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
- Induction of mucosal homing markers on HIV-specific T-cells as assessed by flow cytometric assays of peripheral blood samples [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Multiparameter flow cytometric analyses of dendritic and NK cells in PBMCs, analysis of cytokines and chemokines using a multiplex assay of serum, plasma, semen, cervical secretions and dried blood spots, and gene expression analysis of RNA from PBMCs. [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Flow cytometric analysis of T-cell activation and subsets detected in specimens collected from the rectum, semen, or cervix [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Adenovirus-specific T-cell response rates detected in specimens collected from the rectum, semen, or cervix as assessed by IFN-γ ELISpot assay and/or flow cytometry [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- HIV-specific IgA and IgG responses in saliva, cervical secretions, semen, which may include neutralizing activity [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
|Study Start Date:||May 2011|
|Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
Experimental: Group 1
Participants will receive three injections of VRC-HIVDNA-016-00-VP at Months, 0, 1, and 2 and one injection of VRCHIVADV014-00-VP at Month 6.
Composed of six DNA plasmids in equal concentrations that encode Gag, Pol, and Nef from clade B (strains HXB2, NL4-3, NY5/BRU) and the HIV-1 Env glycoproteins from clade A (strain 92rw020), clade B (strains HXB2/BaL), and clade C (strain 97ZA012). Vaccine will be administered intramuscularly (IM) in the deltoid via needle-free Biojector.Biological: VRCHIVADV014-00-VP
A mixture of 4 recombinant serotype 5 adenoviral replication deficient vectors, each expressing HIV-1 proteins (clade B Gag-Pol fusion, clade A Env, clade B Env, clade C Env). Administered IM via needle and syringe.
The worldwide HIV/AIDS epidemic may only be controlled through development of a safe and effective vaccine that will prevent HIV infection. DNA vaccines are inexpensive to construct, readily produced in large quantities, and stable for long periods of time. This study will evaluate the safety and immunogenicity of an experimental multiclade HIV vaccine, VRC-HIVDNA016-00-VP, followed by a similarly structured adenovirus-vectored vaccine boost, VRC-HIVADV014-00-VP, in HIV uninfected adults. The DNA plasmids in both the vaccines code for proteins from HIV subtypes A, B, and C, which together represent 90% of new HIV infections in the world. The study's primary objective is to investigate the ability of a 6-plasmid DNA prime followed by a rAd5 boost to elicit HIV-specific cellular immune responses at mucosal surfaces.
This study will last 12 months and participants will visit the clinic 15 times. Participants will receive three injections of the VRC-HIVDNA016-00-VP vaccine at Months 0, 1, and 2 followed by an injection of VRC-HIVADV014-00-VP at Month 6. All injections will be given in the upper arm. At study visits participants will have a physical, medical history taken, blood collection, and risk reduction counseling. At some visits, rectal biopsies (via anoscopy or, optionally, by flexible sigmoidoscopy), saliva, semen, cervical and/or vaginal fluid samples will also be collected. Pregnancy testing for women will be done prior to each vaccination and study procedure.
Participants will be contacted by study staff once a year for 5 years after the initial study visit for follow-up health and safety monitoring.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00955006
|United States, Washington|
|Seattle Vaccine and Prevention CRS|
|Seattle, Washington, United States, 98109-1024|
|Study Chair:||Janine Maenza||Fred Hutchinson Cancer Research Center|