title: Issues for improving multiplasmid DNA vaccines for HIV-1.
abstract: Since the first reports of plasmid vaccines, there have been substantial changes made to the design of plasmid backbones, as well as to the antibiotic resistance markers chosen for clinical vectors compared with first generation vectors. These changes aid manufacturing, production and scale up and at the same time aid conceptual safety by limiting the ability of the vaccines to transfer useful genetic selection genes to other bacterial infectious agents. In contrast, there has been little change to the original promoters or polyadenlyation tracts in the last decade. We have learned that these first generation plasmid vaccines for HIV-1 appear very well tolerated in humans. However, while safe and immunogenic, improving the immune potency of DNA vaccines is a critical goal for this technology. The combination of antigens used should be carefully examined for possible immune interference. Such interference may only become apparent when each component of the vaccine is tested individually. This interference also suggests one mechanism of immune pathogenesis possibly by HIV-1. Optimization of the immune response can come through manipulation of the transfection efficiency, expression or through the use of various T cell and B cell plasmid adjuvants. It is likely that the combination of such advancements will significantly improve the clinical phenotype of this important vaccine modality.
authors: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Karuppiah
authors: K
authors: Muthumani
authors: Sagar
authors: S
authors: Kudchodkar
authors: Donghui
authors: D
authors: Zhang
authors: M L
authors: ML
authors: Bagarazzi
authors: Joseph J
authors: JJ
authors: Kim
authors: J D
authors: JD
authors: Boyer
authors: Velpandi
authors: V
authors: Ayyavoo
authors: George N
authors: GN
authors: Pavlakis
authors: David B
authors: DB
authors: Weiner
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics; D000818:Animals; D003062:Codon / Q000235:genetics; D004306:Dose-Response Relationship, Immunologic; D015195:Drug Design; D004351:Drug Resistance / Q000235:genetics; D005813:Genes, Synthetic; D015757:Genes, rev; D016334:Genes, vpr; D005818:Genetic Engineering; D005822:Genetic Vectors / Q000235:genetics*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D011401:Promoter Regions, Genetic; D012449:Safety; D012641:Selection, Genetic; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014611:Vaccination; D019444:Vaccines, DNA / Q000235:genetics; D014614:Vaccines, Synthetic / Q000235:genetics
chemical_list: D016915:AIDS Vaccines; D003062:Codon; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D007371:Interferon-gamma