Design, construction, and characterization of a dual-promoter multigenic DNA vaccine directed against an HIV-1 subtype C/B' recombinant.
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.
Huang
Yaoxing
Y
Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA.
Chen
Zhiwei
Z
Zhang
Wenyong
W
Gurner
Deborah
D
Song
Yang
Y
Gardiner
David F
DF
Ho
David D
DD
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D000818:Animals; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002460:Cell Line; D003001:Cloning, Molecular; D004797:Enzyme-Linked Immunosorbent Assay; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015693:Gene Products, nef / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015684:Gene Products, pol / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015696:Gene Products, tat / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015483:HIV Antibodies / Q000097:blood; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012191:Retroviridae Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D016915:AIDS Vaccines; D015686:Gene Products, env; D015683:Gene Products, gag; D015693:Gene Products, nef; D015684:Gene Products, pol; D015696:Gene Products, tat; D015483:HIV Antibodies; D012191:Retroviridae Proteins; D019444:Vaccines, DNA; D007371:Interferon-gamma