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J Acquir Immune Defic Syndr. 2008 Apr 1;47(4):403-11. doi: 10.1097/QAI.0b013e3181651b9d.

Design, construction, and characterization of a dual-promoter multigenic DNA vaccine directed against an HIV-1 subtype C/B' recombinant.

Author information

1
Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA.

Abstract

An effective vaccine against HIV-1 is generally considered the best hope for controlling the raging AIDS pandemic. As a part of our AIDS vaccine development effort, we constructed a dual-promoter plasmid capable of high-level expression of 2 independent transgenes. HIV-1 gag, pol, env, nef, and tat from a primary subtype C/B' CCR5-tropic HIV-1 were "codon" optimized, modified to eliminate known functional activity, and assembled using an overlapping polymerase chain reaction into 2 plasmids: ADVAX-I (containing env and gag) and ADVAX-II (containing pol and nef-tat). These 2 dual-promoter candidate vaccines showed levels of HIV-1 gene expression comparable to those observed with single-gene plasmids in vitro. Importantly, immunization of mice with these vaccine constructs resulted in dose-dependent multigenic CD4 and CD8 T-cell responses equivalent to those provided by vaccination with single-gene plasmids. With input from the US Food and Drug Administration, ADVAX-I and ADVAX-II have since been combined as a single candidate DNA vaccine, ADVAX. A phase 1 clinical trial of this product has been successfully completed, and its use in prime-boost studies is now underway.

PMID:
18209683
DOI:
10.1097/QAI.0b013e3181651b9d
[Indexed for MEDLINE]

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