期刊
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
卷 47, 期 4, 页码 403-411出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAI.0b013e3181651b9d
关键词
ADVAX; AIDS; dual promoter DNA vaccine; HIV; vaccine
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 I clinical trial of this product has been successfully completed, and its use in prime-boost studies is now underway.
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