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Graham, Barney S. ; Koup, Richard A. ; Roederer, Mario ; Bailer, Robert T. ; Enama, Mary E. ; Moodie, Zoe ; Martin, Julie E. ; McCluskey, Margaret M. ; Chakrabarti, Bimal K. ; Lamoreaux, Laurie ; Andrews, Charla A. ; Gomez, Phillip L. ; Mascola, John R.
The Journal of infectious diseases, 12/2006, Letnik: 194, Številka: 12Journal Article
Background. Gene‐based vaccine delivery is an important strategy in the development of a preventive vaccine for acquired immunodeficiency syndrome (AIDS). Vaccine Research Center (VRC) 004 is the first phase 1 dose‐escalation study of a multiclade HIV‐1 DNA vaccine. Methods. VRC‐HIVDNA009‐00‐VP is a 4‐plasmid mixture encoding subtype B Gag‐Pol‐Nef fusion protein and modified envelope (Env) constructs from subtypes A, B, and C. Fifty healthy, uninfected adults were randomized to receive either placebo (n=10) or study vaccine at 2 mg (n=5), 4 mg (n=20), or 8 mg (n=15) by needle‐free intramuscular injection. Humoral responses (measured by enzyme‐linked immunosorbant assay, Western blotting, and neutralization assay) and T cell responses (measured by enzyme‐linked immunospot assay and intracellular cytokine staining after stimulation with antigen‐specific peptide pools) were measured. Results. The vaccine was well tolerated and induced cellular and humoral responses. The maximal CD4+ and CD8+ T cell responses occurred after 3 injections and were in response to Env peptide pools. The pattern of cytokine expression by vaccine‐induced HIV‐specific T cells evolved over time, with a diminished frequency of interferon‐γ–producing T cells and an increased frequency of interleukin‐2–producing T cells at 1 year. Conclusions. DNA vaccination induced antibody to and T cell responses against 3 major HIV‐1 subtypes and will be further evaluated as a potential component of a preventive AIDS vaccine regimen.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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