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) and gene fusions to its capsid decoration protein gpD as reagent tools for tackling disease, particularly when fused to cathelicidins or defensins retaining biological activity. We briefly review the formative studies for considering that phage representatives could serve as reagent tools helping to combat disease. This includes early ideas for “phage therapy” and the use of “display or vector” phages for vaccine generation and bioassays. We compare gene-fusion lytic display systems where the fusion display gene is integrated within the viral genome with a surrogate system that exogenously provides the fusion-display protein for addition to phage capsid. Finally, we discuss the potential for vaccine vector phage particles, which are essentially sheathed DNA vaccines encapsulated within an environmentally protective capsid. We show how it is easily possible to produce fully coated LDP serving as single epitope vaccines, or antimicrobials, or to produce partially coated LDP without any complex bacteriophage genetic engineering, making the system available to all. We show that multiple, single epitope LDP vaccine reagents can be generated in a single infection lysate. We provide a system whereby either intracellular phage-plasmid substitution recombination, or by cloning, can generate sheathed DNA vaccine particles, termed LDNAP that have the advantage of a high-level eukaryotic expression cassette without incorporating plasmid resistance elements or other genes.