Immune Response to an HIV DNA Plasmid Vaccine Prime Followed by Adenovirus Boost in HIV-uninfected Individuals

NCT00955006 | Completed Phase 1

• 2 other identifiers: HVTN 07610625
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV Infections

Keywords

HIV Seronegativity; HIV Preventive Vaccine

Outcome Measures

Primary Outcomes (1)

• 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

  Throughout study

Secondary Outcomes (6)

• Local and systemic reactogenicity signs and symptoms, adverse events and severe adverse events.

  Throughout study

• Induction of mucosal homing markers on HIV-specific T-cells as assessed by flow cytometric assays of peripheral blood samples

  Throughout study

• 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.

  Throughout study

• Flow cytometric analysis of T-cell activation and subsets detected in specimens collected from the rectum, semen, or cervix

  Throughout study

• 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

  Throughout study

Study Arms (1)

Group 1

EXPERIMENTAL

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.

Biological: VRC-HIVDNA-016-00-VP; Biological: VRCHIVADV014-00-VP

Interventions

VRC-HIVDNA-016-00-VP BIOLOGICAL

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.

Group 1

VRCHIVADV014-00-VP BIOLOGICAL

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.

Group 1

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Access to participating HVTN CRS and willingness to be followed for the planned duration of the study
• Ability and willingness to provide informed consent
• Assessment of understanding: participant demonstrates understanding of this study and the Step Study results; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly
• Willingness to receive HIV test results
• Willingness to discuss HIV infection risks, amenable to HIV risk reduction counseling, committed to maintaining behavior consistent with low risk of HIV exposure through the last required clinic visit, and willing to continue annual follow-up contact after the last required clinic visit, for a total of 5 years following enrollment
• Agrees not to enroll in another study of an investigational research agent prior to completion of last required protocol clinic visit (excludes annual follow-up contact for safety surveillance)
• Assessed by clinic staff as being at "low risk" for HIV infection. More information on this criterion can be found in the protocol.
• Good general health as shown by medical history, physical exam, and screening laboratory tests. More information on this criterion can be found in the protocol.
• Neutralizing antibody titers of Ad5 less than 1:18
• Hemoglobin equal to or greater than 11.0 g/dL for participants who were born female, 12.5 g/dL for participants who were born male
• White blood cell (WBC) count = 3,300 to 12,000 cells/mm\^3
• Total lymphocyte count equal to or greater than 800 cells/mm\^3
• Remaining differential either within institutional normal range or accompanied by site physician approval
• Platelets = 125,000 to 550,000/mm\^3
• Prothrombin time (PT) less than 1.5 and partial thromboplastin time (PTT) less than 1.25 greater than upper limits of normal

You may not qualify if:

• Excessive daily alcohol use or frequent binge drinking or chronic marijuana abuse or any other use of illicit drugs within the past 12 months
• A history of newly acquired syphilis, gonorrhea, non-gonococcal urethritis, herpes simplex virus type 2 (HSV2), Chlamydia, pelvic inflammatory disease (PID), trichomonas, mucopurulent cervicitis, epididymitis, proctitis, lymphogranuloma venereum, chancroid, or hepatitis B in the past 12 months
• HIV vaccine(s) received in a prior HIV vaccine trial. For potential participants who have received control/placebo in an HIV vaccine trial, the HVTN 076 PSRT will determine eligibility on a case-by-case basis.
• Experimental vaccine(s) received within the last 5 years in a prior vaccine trial. More information on this criterion can be found in the protocol.
• Immunosuppressive medications received within 168 days before first vaccination (eg, oral/parenteral corticosteroids, and/or cytotoxic medications). People taking corticosteroid nasal spray for allergic rhinitis and topical corticosteroids for mild, uncomplicated dermatitis are not excluded.
• Abnormality of the colorectal mucosa, or significant colorectal symptom(s), which in the opinion of the clinician represents a contraindication to biopsy (including but not limited to presence of any unresolved injury, infectious or inflammatory condition of the local mucosa, and presence of hemorrhoids)
• Blood products received within 120 days before first vaccination
• Immunoglobulin received within 60 days before first vaccination
• Live attenuated vaccines other than influenza vaccine received within 30 days before first vaccination or scheduled within 14 days after vaccination (e.g., measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever)
• Influenza vaccine or any vaccines that are not live attenuated vaccines received within 14 days prior to first vaccination or scheduled within 14 days after vaccination (e.g., influenza, tetanus, pneumococcal, hepatitis A or B)
• Investigational research agents received within 30 days before first vaccination
• Intent to participate in another study of an investigational research agent during the planned duration of the study
• Allergy treatment with antigen injections within 30 days before first vaccination or scheduled within 14 days after injection
• Current anti-tuberculosis (TB) prophylaxis or therapy
• Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. More information on this criterion can be found in the protocol.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Seattle Vaccine and Prevention CRS

Seattle, Washington, 98109-1024, United States

Location

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Janine Maenza

  Fred Hutchinson Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2009
• First Posted: August 7, 2009
• Study Start: May 1, 2011
• Primary Completion: September 1, 2013
• Study Completion: November 22, 2017
• Last Updated: October 14, 2021

Record last verified: 2021-10

Locations

US (1)