Potential Vaccine or Antimicrobial Reagents: Simple Systems for Producing Lambda Display Particles (LDP) and Sheathed Lambda DNA Vaccine Particles (LDNAP)

The focus of this study was to explore phage display systems employing bacteriophage lambda (λ) gene fusions to its capsid decoration protein gpD as reagent tools for tackling disease. The biological activity of gpD-fusions was examined by testing for the retained antimicrobial toxicity of cathelicidins or defensins fused to gpD. Our previous finding that only COOH fusions of either cathelicidins or defensins to gpD were toxigenic was expanded to show that only the reduced form of fused defensin antimicrobial polypeptides was found to be toxigenic. Compared in review are gene-fusion lytic display systems (where the fusion-display gene is integrated within the viral genome) with a surrogate system, employed herein, that exogenously provides the fusion-display protein for addition to phage capsid. It is easily possible to produce fully coated lambda display particles (LDP) serving as single epitope vaccines (SEV), or antimicrobials, or to produce partially coated LDP without any complex bacteriophage genetic engineering, making the system available to all. The potential to build vaccine vector phage particles (LDNAP) comprising essentially sheathed DNA vaccines encapsulated within an environmentally protective capsid is described. LDNAP are produced by introducing a cassette into the phage genome either by phage-plasmid recombination or cloning. The cassette carries a high-level eukaryotic expression promoter driving transcription of the vaccine candidate gene and is devoid of plasmid resistance elements.