title: Enhancement of immune responses to an HIV gp120 DNA vaccine by fusion to TNF alpha cDNA.
abstract: DNA vaccines have considerable potential for disease prophylaxis and therapy, but are generally poorly immunogenic. A number of means of enhancing immunogenicity have been assessed, including the co-expression of cytokines, the use of heterologous prime-boost regimes, and the addition of more conventional adjuvants. In this study we have assessed the effects on gp120 DNA immunogenicity of in-frame fusion of tumor necrosis factor alpha DNA to DNA encoding a large fragment of HIV gp120. The studies were performed using a DNA prime, protein boost regime and a heterologous boosting protein. Fusion of TNFalpha DNA enhanced Th1 related immune responses against both the priming and the boosting gp120. In-frame fusion of interferon gamma-encoding DNA at the 5' end of the chimeric molecule, to create a tripartite fusion, had no additional effect on immunogenicity.
authors.affiliation: Unit of Infection and Immunity, Division of Genomic Medicine, University of Sheffield School of Medicine and Biomedical Science, Beech Hill Rd., Sheffield S10 2RX, UK.
authors.forename: Sonali
authors.initials: S
authors.lastname: Nimal
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Heath
authors.forename: Mark S
authors.initials: MS
authors.lastname: Thomas
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000276:Adjuvants, Immunologic; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015483:HIV Antibodies / Q000097:blood*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D016207:Cytokines; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D019444:Vaccines, DNA