title: A genome-based functional screening approach to vaccine development that combines in vitro assays and DNA immunization.
abstract: A two-step screening strategy was developed to identify strong immunogenic polypeptides with putative vaccine and/or adjuvant activity. In the first step, a mycobacterial genomic DNA library was screened in vitro to identify plasmids encoding polypeptides that stimulate splenocytes from mycobacteria-immunized mice and T cells from PPD-positive healthy donors to produce interferon-gamma. In the second step, plasmids were selected for their ability to induce protective immunity in a mouse model of tuberculosis following DNA immunization. The potential of this approach is illustrated by the identification of a panel of immunogenic polypeptides that may be used to engineer a new generation of vaccines.
authors.affiliation: Genesis Research and Development, 1 Fox Street, Parnell, Auckland, New Zealand. adelcayre@anosys.com
authors.forename: Alain
authors.initials: A
authors.lastname: Delcayre
authors.forename: John S
authors.initials: JS
authors.lastname: Peake
authors.forename: Damian J
authors.initials: DJ
authors.lastname: White
authors.forename: Shining
authors.initials: S
authors.lastname: Yuan
authors.forename: Megan K
authors.initials: MK
authors.lastname: McDonald
authors.forename: Andrew
authors.initials: A
authors.lastname: Liang
authors.forename: Paul L
authors.initials: PL
authors.lastname: Tan
authors.forename: James D
authors.initials: JD
authors.lastname: Watson
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D019556:COS Cells; D016207:Cytokines / Q000096:biosynthesis; D004269:DNA, Bacterial / Q000096:biosynthesis / Q000276:immunology / Q000302:isolation & purification; D004353:Drug Evaluation, Preclinical; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015723:Gene Library; D016678:Genome; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology; D009161:Mycobacterium / Q000276:immunology / Q000378:metabolism; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D004269:DNA, Bacterial; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA