Open AccessDesign, Construction, and Characterization of a Dual-Promoter Multigenic DNA Vaccine Directed Against an HIV-1 Subtype C/B′ Recombinant
Author(s) -
Yaoxing Huang,
Zhiwei Chen,
Wenyong Zhang,
Deborah Gurner,
Yang Song,
David F. Gardiner,
David D. Ho
Publication year - 2008
Publication title -
journal of acquired immune deficiency syndromes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.162
H-Index - 157
eISSN - 1944-7884
pISSN - 1525-4135
DOI - 10.1097/qai.0b013e3181651b9d
Subject(s) - plasmid , virology , dna vaccination , biology , hiv vaccine , recombinant dna , gene , lentivirus , transgene , vaccination , genetics , human immunodeficiency virus (hiv) , vaccine trial , viral disease
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.