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Safety and immunogenicity of a replication-defective adenovirus type 5 HIV vaccine in Ad5-seronegative persons: a randomized clinical trial (HVTN 054).

Publication ,  Journal Article
Peiperl, L; Morgan, C; Moodie, Z; Li, H; Russell, N; Graham, BS; Tomaras, GD; De Rosa, SC; McElrath, MJ; NIAID HIV Vaccine Trials Network
Published in: PLoS One
October 27, 2010

BACKGROUND: Individuals without prior immunity to a vaccine vector may be more sensitive to reactions following injection, but may also show optimal immune responses to vaccine antigens. To assess safety and maximal tolerated dose of an adenoviral vaccine vector in volunteers without prior immunity, we evaluated a recombinant replication-defective adenovirus type 5 (rAd5) vaccine expressing HIV-1 Gag, Pol, and multiclade Env proteins, VRC-HIVADV014-00-VP, in a randomized, double-blind, dose-escalation, multicenter trial (HVTN study 054) in HIV-1-seronegative participants without detectable neutralizing antibodies (nAb) to the vector. As secondary outcomes, we also assessed T-cell and antibody responses. METHODOLOGY/PRINCIPAL FINDINGS: Volunteers received one dose of vaccine at either 10(10) or 10(11) adenovector particle units, or placebo. T-cell responses were measured against pools of global potential T-cell epitope peptides. HIV-1 binding and neutralizing antibodies were assessed. Systemic reactogenicity was greater at the higher dose, but the vaccine was well tolerated at both doses. Although no HIV infections occurred, commercial diagnostic assays were positive in 87% of vaccinees one year after vaccination. More than 85% of vaccinees developed HIV-1-specific T-cell responses detected by IFN-γ ELISpot and ICS assays at day 28. T-cell responses were: CD8-biased; evenly distributed across the three HIV-1 antigens; not substantially increased at the higher dose; and detected at similar frequencies one year following injection. The vaccine induced binding antibodies against at least one HIV-1 Env antigen in all recipients. CONCLUSIONS/SIGNIFICANCE: This vaccine appeared safe and was highly immunogenic following a single dose in human volunteers without prior nAb against the vector. TRIAL REGISTRATION: ClinicalTrials.gov NCT00119873.

Duke Scholars

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

October 27, 2010

Volume

5

Issue

10

Start / End Page

e13579

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Placebos
  • Male
  • Humans
  • General Science & Technology
  • Female
  • Enzyme-Linked Immunosorbent Assay
  • Double-Blind Method
  • Defective Viruses
  • Antibodies, Neutralizing
 

Citation

APA
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MLA
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Peiperl, L., Morgan, C., Moodie, Z., Li, H., Russell, N., Graham, B. S., … NIAID HIV Vaccine Trials Network. (2010). Safety and immunogenicity of a replication-defective adenovirus type 5 HIV vaccine in Ad5-seronegative persons: a randomized clinical trial (HVTN 054). PLoS One, 5(10), e13579. https://doi.org/10.1371/journal.pone.0013579
Peiperl, Laurence, Cecilia Morgan, Zoe Moodie, Hongli Li, Nina Russell, Barney S. Graham, Georgia D. Tomaras, Stephen C. De Rosa, M Juliana McElrath, and NIAID HIV Vaccine Trials Network. “Safety and immunogenicity of a replication-defective adenovirus type 5 HIV vaccine in Ad5-seronegative persons: a randomized clinical trial (HVTN 054).PLoS One 5, no. 10 (October 27, 2010): e13579. https://doi.org/10.1371/journal.pone.0013579.
Peiperl L, Morgan C, Moodie Z, Li H, Russell N, Graham BS, et al. Safety and immunogenicity of a replication-defective adenovirus type 5 HIV vaccine in Ad5-seronegative persons: a randomized clinical trial (HVTN 054). PLoS One. 2010 Oct 27;5(10):e13579.
Peiperl, Laurence, et al. “Safety and immunogenicity of a replication-defective adenovirus type 5 HIV vaccine in Ad5-seronegative persons: a randomized clinical trial (HVTN 054).PLoS One, vol. 5, no. 10, Oct. 2010, p. e13579. Pubmed, doi:10.1371/journal.pone.0013579.
Peiperl L, Morgan C, Moodie Z, Li H, Russell N, Graham BS, Tomaras GD, De Rosa SC, McElrath MJ, NIAID HIV Vaccine Trials Network. Safety and immunogenicity of a replication-defective adenovirus type 5 HIV vaccine in Ad5-seronegative persons: a randomized clinical trial (HVTN 054). PLoS One. 2010 Oct 27;5(10):e13579.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

October 27, 2010

Volume

5

Issue

10

Start / End Page

e13579

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Placebos
  • Male
  • Humans
  • General Science & Technology
  • Female
  • Enzyme-Linked Immunosorbent Assay
  • Double-Blind Method
  • Defective Viruses
  • Antibodies, Neutralizing