A λ Phage Platform for Successful Therapeutic Display of Protein Antigens

We have developed a vector platform for delivery of foreign peptides by genetic modification of the temperate lambda (λ) bacteriophage. This delivery platform is capable of displaying peptides or proteins on either terminus of the structural λ head protein D, present in ~ 420 copies per phage particle, and λ side tail fiber (Stf), present at 12 copies per phage particle. Proteins and peptides can be easily fused for display through the low-cost and high-efficiency methods of recombineering and λ prophage induction for recombinant phage preparation described here. To improve this vector technology for use in antigen selection and immunotherapy, we introduced several mutations in the bacterial host and resident prophage λ that improve engineering, induction, phage stability, yield, fusion protein accommodation capacity, and longevity in animal systems. We tested the ability of this λ display system to identify useful antigens and generate antibodies in a mouse model. We report its success as a new technology for both applications: the selection and delivery of therapeutic peptides and proteins.