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

Area of Science:

• Bacteriophage display systems
• Molecular biology
• Vaccine development

Background:

• Bacteriophage lambda (λ) gene fusions to capsid protein gpD offer potential disease-targeting tools.
• Previous work indicated COOH fusions of cathelicidins or defensins to gpD were toxigenic.

Purpose of the Study:

• To explore phage display systems using bacteriophage lambda (λ) gene fusions to gpD for disease applications.
• To examine the biological activity of gpD-fusions, specifically antimicrobial toxicity.
• To compare gene-fusion lytic display systems with a surrogate system for producing display particles.

Main Methods:

• Examined biological activity of gpD-fusions by testing antimicrobial toxicity of cathelicidins or defensins.
• Expanded previous findings to show reduced form of fused defensin antimicrobial polypeptides are toxigenic.
• Compared gene-fusion lytic display systems with a surrogate system providing exogenous fusion-display protein.

Main Results:

• Only the reduced form of fused defensin antimicrobial polypeptides demonstrated toxigenicity.
• Developed a surrogate system for exogenous production of fusion-display proteins, enabling easy production of fully or partially coated lambda display particles (LDP).
• Demonstrated the potential to create vaccine vector phage particles (LDNAP) encapsulating DNA vaccines within a protective capsid.

Conclusions:

• The study presents a versatile bacteriophage lambda (λ) display system for developing antimicrobials and vaccines.
• The surrogate system simplifies the production of LDPs (lambda display particles) for single epitope vaccines (SEV) or antimicrobials.
• The development of LDNAP (lambda DNA vaccine phage particles) offers a novel approach for DNA vaccine delivery.