Safety of and Immune Response to a DNA HIV Vaccine Followed By an Adenoviral Vector HIV Vaccine in Healthy Adults

Brief Summary

Official Title: “A Phase II Clinical Trial to Evaluate the Safety and Immunogenicity of a Multiclade HIV-1 DNA Plasmid Vaccine, VRC-HIVDNA016-00-VP, Followed By a Multiclade Recombinant Adenoviral Vector HIV-1 Vaccine Boost, VRC-HIVADV014-00-VP, in HIV-1 Uninfected Adult Participants”

The purpose of the study is to determine the safety of and immune response to a DNA HIV vaccine followed by an adenoviral vector HIV vaccine in HIV uninfected adults.

  • Study Type: Interventional
  • Study Design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Prevention
  • Study Primary Completion Date: February 2008

Detailed Clinical Trial Description

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. Participants in this study will be recruited in North America, South America, and Africa.

Each volunteer will participate in the study for 36 months. Participants will be randomly assigned to one of two groups. Group 1 participants will receive the DNA HIV vaccine at study entry and at Months 1 and 2. At Month 6, Group 1 participants will receive an injection of the adenoviral vector HIV vaccine. Group 2 participants will receive placebo at study entry and Months 1, 2, and 6. There will be 17 study visits, which will occur at study entry and every 2 weeks thereafter until Day 70; at Month 6 and every 2 weeks thereafter until Day 210; and Months 9.5, 12, 18, 24, 30, and 36. A physical exam, adverse events reporting, HIV and pregnancy prevention counseling, and medication history will occur at each visit. Blood and urine collection will occur at selected visits.

Interventions Used in this Clinical Trial

  • Biological: VRC-HIVDNA016-00-VP
    • 4 mg administered in deltoid
  • Biological: VRC-HIVADV014-00-VP
    • 1 x 10^10 PU administered in deltoid
  • Biological: VRC-HIVDNA016-00-VP placebo
    • 1 mL administered at study entry and Months 1 and 2
  • Biological: VRC-HIVADV014-00-VP placebo
    • 1 mL administered at Month 6

Arms, Groups and Cohorts in this Clinical Trial

  • Experimental: 1
    • DNA HIV vaccine administered at study entry and at Months 1 and 2 and adenoviral vector HIV vaccine administered at Month 6
  • Placebo Comparator: 2
    • DNA HIV vaccine placebo administered at study entry and at Months 1 and 2 and adenoviral vector HIV vaccine placebo administered at Month 6

Outcome Measures for this Clinical Trial

Primary Measures

  • Local and systemic adverse reactions
    • Time Frame: Measured after each injection and for 12 months after the first injection
      Safety Issue?: Yes
  • Unfractionated IFN-γ ELISpot responses to HIV-1 peptide pools as performed by the VRC laboratory
    • Time Frame: Measured at Day 196
      Safety Issue?: No
  • Unfractionated IFN-γ ELISpot responses to HIV-1 peptide pools as performed by the FHCRC laboratory
    • Time Frame: Measured at Day 210
      Safety Issue?: No
  • CD4 and CD8 T cell responses to HIV-1 peptide pools as measured by flow cytometry-based intracellular cytokine staining (ICS) assay as performed by the VRC laboratory
    • Time Frame: Measured at Day 196
      Safety Issue?: No
  • CD4 and CD8 T cell responses to HIV-1 peptide pools as measured by flow cytometry-based ICS assay as performed by the FHCRC laboratory
    • Time Frame: Measured at Day 210
      Safety Issue?: No

Secondary Measures

  • Humoral immune response to HIV-1 as measured by neutralizing antibody and binding assays
    • Time Frame: Measured through Month 36
      Safety Issue?: No
  • Unfractionated IFN-γ ELISpot responses to HIV-1 as performed by the FHCRC or the VRC laboratories
    • Time Frame: Measured at Days 70, 210, and 364
      Safety Issue?: No
  • CD4 and CD8 T cell responses to HIV-1 as measured by flow cytometry-based ICS assay as performed by the FHCRC or the VRC laboratories
    • Time Frame: Measured at Days 70, 210, and 364
      Safety Issue?: No
  • Vaccine-induced HIV-specific T cell responses to individual peptide pools as measured by IFN-γ ELISpot and ICS as performed by the FHCRC or the VRC laboratories
    • Time Frame: Measured through Month 36
      Safety Issue?: No
  • Cross-clade cellular immune responses to HIV-1 Gag-Pol-Nef peptides from clades A and C as assessed by IFN-γ ELISpot and ICS assays as performed by the FHCRC or the VRC laboratories
    • Time Frame: Measured through Month 36
      Safety Issue?: No

Criteria for Participation in this Clinical Trial

Inclusion Criteria

  • HIV uninfected
  • Has 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
  • Willing to use acceptable forms of contraception
  • Completed at least 12 years of schooling (South African participants only)

Exclusion Criteria

  • 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 tuberculosis prophylaxis or therapy
  • Clinically significant medical condition, abnormal physical exam findings, abnormal laboratory results, or past medical history that may affect current health
  • Any medical, psychiatric, or social condition that would interfere with the study. More information about this criterion can be found in the protocol.
  • Any job-related responsibility that would interfere with the study
  • Serious adverse reaction to vaccines. A person who had an adverse reaction to pertussis vaccine as a child is not excluded.
  • Autoimmune disease or immunodeficiency
  • Active syphilis infection
  • Unstable asthma
  • Diabetes mellitus type 1 or 2
  • Thyroid disease requiring treatment
  • Serious angioedema within the past 3 years
  • Uncontrolled hypertension
  • Bleeding disorder
  • Cancer. If a participant has had surgery to remove the cancer and, in the opinion of the investigator, the cancer is not likely to recur during the study period, the participant is not excluded.
  • Seizure disorder
  • Asplenia
  • Mental illness that would interfere with compliance with the protocol
  • Other conditions that, in the judgment of the investigator, would interfere with the study
  • Pregnant or breastfeeding

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 50 Years

Are Healthy Volunteers Accepted for this Clinical Trial: Accepts Healthy Volunteers

Clinical Trial Investigator Information

  • Lead Sponsor
    • National Institute of Allergy and Infectious Diseases (NIAID)
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Michael Keefer, MD, Study Chair, University of Rochester
    • Gavin Churchyard, MBBCh, FCP, MMed, PhD, Study Chair, Aurum Health Research Limited

References

Esparza J, Osmanov S. HIV vaccines: a global perspective. Curr Mol Med. 2003 May;3(3):183-93. Review.

Gaschen B, Taylor J, Yusim K, Foley B, Gao F, Lang D, Novitsky V, Haynes B, Hahn BH, Bhattacharya T, Korber B. Diversity considerations in HIV-1 vaccine selection. Science. 2002 Jun 28;296(5577):2354-60. Review.

Moore JP, Parren PW, Burton DR. Genetic subtypes, humoral immunity, and human immunodeficiency virus type 1 vaccine development. J Virol. 2001 Jul;75(13):5721-9. Review. No abstract available.

Stratov I, DeRose R, Purcell DF, Kent SJ. Vaccines and vaccine strategies against HIV. Curr Drug Targets. 2004 Jan;5(1):71-88. Review.

Source

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http://clinicaltrialsfeeds.org/clinical-trials/show/NCT00125970