Safety of and Immune Response to a DNA HIV Vaccine Followed By Boosting With One of Two Serotypes of Adenoviral Vector HIV Vaccine in Healthy Adults

NCT00472719 | Completed Phase 1 DMC

• 2 other identifiers: HVTN 07210517
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to determine the safety of and immune response to an experimental DNA HIV vaccine followed by boosting with either an experimental adenoviral vector HIV vaccine of serotype 5 or 35 in HIV uninfected adults. This study will also determine the safety of and immune response to an adenoviral vector HIV vaccine of serotype 5 followed by a booster of an adenoviral vector of serotype 35, or vice versa, in HIV uninfected adults.

Conditions

HIV Infections

Keywords

HIV Seronegativity; HIV Preventive Vaccine; Adenovirus

Outcome Measures

Primary Outcomes (4)

• Safety and tolerability of HIV-1 recombinant Clade A env DNA, rAd5, and rAd35 vaccines in participants with pre-existing immunity to Ad5

  at 9 to 12 months

• Magnitude and frequency of immune responses between the adenoviral vaccines following DNA prime, assessed by enzyme-linked immunospot (ELISpot) responses, intracellular cytokine staining (ICS) T-cell responses, and HIV-1 antibody assays

  at 4 weeks following fourth vaccination

• Immunogenicity of recombinant HIV-1 Clade A env rAd35 vaccine following a recombinant rAd5 prime, assessed by ELISpot responses, ICS T-cell responses, and HIV-1 antibody assays

  at 4 weeks following the second vaccination

• Immunogenicity of recombinant HIV-1 Clade A env rAd5 vaccine following a recombinant rAd35, assessed by ELISpot responses, ICS T-cell responses, and HIV-1 antibody assays

  at 4 weeks following the second vaccination

Secondary Outcomes (3)

• Rank of HIV-1 rAd5/rAd35, rAd35/rAd5, DNA/rAd5, and DNA/rAd35 regimens based on ELISpot responses, ICS T-cell responses, and HIV-1 antibody assays

  at 4 weeks after second vaccination for Groups 1 and 2, and at 4 weeks after fourth vaccination for Groups 3 and 4

• Immunogenicity of HIV-1 rAd35 vaccine given as a prime assessed by ELISpot responses, ICS T-cell responses, and HIV-1 antibody assays

  at 4 weeks following first vaccination

• Immunogenicity of HIV-1 rAd5 vaccine given as a prime, assessed by ELISpot responses, ICS T-cell responses, and HIV-1 antibody assays

  at 4 weeks following first vaccination

Study Arms (4)

1

EXPERIMENTAL

Participants in this group will receive an injection of the adenoviral vector vaccine VRC-HIVADV027-00VP at study entry and an injection of VRC-HIVADV038-00-VP at Month 3. There will be 9 study visits for this arm.

Biological: VRC-HIVADV027-00-VP; Biological: VRC-HIVADV038-00-VP

2

EXPERIMENTAL

Participants in this group will receive an injection of VRC-HIVADV038-00-VP at study entry and an injection of VRC-HIVADV027-00-VP at Month 3. There will be 9 study visits for this group.

Biological: VRC-HIVADV027-00-VP; Biological: VRC-HIVADV038-00-VP

3

EXPERIMENTAL

Participants in this group will receive an injection of the VRC-HIVDNA044-00-VP vaccine at study entry and Months 1 and 2, followed by an injection of VRC-HIVADV027-00-VPat Month 6. There will be 13 study visits for this group.

Biological: VRC-HIVADV027-00-VP; Biological: VRC-HIVDNA044-00-VP

4

EXPERIMENTAL

Participants in this group will receive an injection of VRC-HIVDNA044-00-VP at study entry and Months 1 and 2, followed by an injection of VRC-HIVADV038-00-VP at Month 6. There will be 13 study visits for this group.

Biological: VRC-HIVADV038-00-VP; Biological: VRC-HIVDNA044-00-VP

Interventions

VRC-HIVADV027-00-VP BIOLOGICAL

Adenoviral vector booster vaccine

1; 2; 3

VRC-HIVADV038-00-VP BIOLOGICAL

Adenovirus vector booster vaccine

1; 2; 4

VRC-HIVDNA044-00-VP BIOLOGICAL

Experimental, multiclade, multigene HIV DNA vaccine

3; 4

Eligibility Criteria

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

You may qualify if:

• HIV-1 and -2 uninfected
• Have access to a participating HIV Vaccine Trials Unit (HVTU) and willing to be followed for the duration of the study
• Willing to receive HIV test results
• Good general health
• Pre-existing adenovirus 5 (Ad5) neutralizing antibody titer of 1:1000 ratio or greater
• Willing to use acceptable forms of contraception from at least 21 days prior to enrollment through the duration of the study

You may not qualify if:

• HIV vaccines in prior HIV vaccine trial
• Immunosuppressive medications within 168 days prior to first study vaccine administration
• Blood products within 120 days prior to first study vaccine administration
• Immunoglobulin within 60 days prior to first study vaccine administration
• Live attenuated vaccines within 30 days prior to first study vaccine administration
• Investigational research agents within 30 days prior to first study vaccine administration
• Subunit or killed vaccines within 14 days prior to first study vaccine administration
• Current anti-tuberculosis prophylaxis or therapy
• Clinically significant medical condition, abnormal physical exam findings, abnormal laboratory results, or past medical history that may affect current health. More information about this criterion can be found in the protocol.
• Any medical, psychiatric, or social condition that would interfere with the study.
• Serious adverse reaction to vaccines. Participants who have had an adverse reaction to pertussis vaccine as a child are not excluded.
• Autoimmune disease or immunodeficiency
• Active syphilis infection. Participants with fully treated syphilis at least 6 months prior to study entry are not excluded.
• Unstable asthma. More information about this criterion can be found in the protocol.
• Diabetes mellitus type 1 or 2. Participants with a history of isolated gestational diabetes are not excluded.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• HIV Vaccine Trials Network: collaborator

Study Sites (7)

Alabama Vaccine CRS

Birmingham, Alabama, 35294, United States

Location

Bridge HIV CRS

San Francisco, California, 94143, United States

Location

Columbia P&S CRS

New York, New York, 10032-3732, United States

Location

New York Blood Center CRS

New York, New York, 10065, United States

Location

University of Rochester Vaccines to Prevent HIV Infection CRS

Rochester, New York, 14642, United States

Location

Vanderbilt Vaccine (VV) CRS

Nashville, Tennessee, 37232-2582, United States

Location

Seattle Vaccine and Prevention CRS

Seattle, Washington, 98109-1024, United States

Location

Related Publications (5)

• Barouch DH, Nabel GJ. Adenovirus vector-based vaccines for human immunodeficiency virus type 1. Hum Gene Ther. 2005 Feb;16(2):149-56. doi: 10.1089/hum.2005.16.149.

  PMID: 15761255 BACKGROUND

• Barouch DH, Pau MG, Custers JH, Koudstaal W, Kostense S, Havenga MJ, Truitt DM, Sumida SM, Kishko MG, Arthur JC, Korioth-Schmitz B, Newberg MH, Gorgone DA, Lifton MA, Panicali DL, Nabel GJ, Letvin NL, Goudsmit J. Immunogenicity of recombinant adenovirus serotype 35 vaccine in the presence of pre-existing anti-Ad5 immunity. J Immunol. 2004 May 15;172(10):6290-7. doi: 10.4049/jimmunol.172.10.6290.

  PMID: 15128818 BACKGROUND

• Cohen P. Immunity's yin and yang. A successful vaccine must first avoid being eliminated by pre-existing immunity before it can promote a protective immune response. IAVI Rep. 2006 Jan-Feb;10(1):1-5. No abstract available.

  PMID: 16625717 BACKGROUND

• Lemckert AA, Sumida SM, Holterman L, Vogels R, Truitt DM, Lynch DM, Nanda A, Ewald BA, Gorgone DA, Lifton MA, Goudsmit J, Havenga MJ, Barouch DH. Immunogenicity of heterologous prime-boost regimens involving recombinant adenovirus serotype 11 (Ad11) and Ad35 vaccine vectors in the presence of anti-ad5 immunity. J Virol. 2005 Aug;79(15):9694-701. doi: 10.1128/JVI.79.15.9694-9701.2005.

  PMID: 16014931 BACKGROUND

• Wu L, Kong WP, Nabel GJ. Enhanced breadth of CD4 T-cell immunity by DNA prime and adenovirus boost immunization to human immunodeficiency virus Env and Gag immunogens. J Virol. 2005 Jul;79(13):8024-31. doi: 10.1128/JVI.79.13.8024-8031.2005.

  PMID: 15956548 BACKGROUND

MeSH Terms

Conditions

HIV Infections; Adenoviridae 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; DNA Virus Infections

Study Officials

• Jonathan Fuchs, MD, MPH

  San Francisco Department of Public Health, University of California, San Francisco

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2007
• First Posted: May 14, 2007
• Study Start: August 1, 2007
• Primary Completion: July 1, 2008
• Study Completion: January 1, 2013
• Last Updated: October 14, 2021

Record last verified: 2021-10

Locations

US (7)