Phage display as a tool for vaccine and immunotherapy development

Abstract

Bacteriophages, or phages, are viruses that specifically infect bacteria and coopt the cellular machinery to create more phage proteins, eventually resulting in the release of new phage particles. Phages are heavily utilized in bioengineering for applications ranging from tissue engineering scaffolds to immune signal delivery. Of specific interest to vaccines and immunotherapies, phages have demonstrated an ability to activate both the innate and adaptive immune systems. The genome of these viral particles can be harnessed for DNA vaccination, or the surface proteins can be exploited for antigen display. More specifically, genes that encode an antigen of interest can be spliced into the phage genome, allowing antigenic proteins or peptides to be displayed by fusion to phage capsid proteins. Phages therefore present antigens to immune cells in a highly ordered and repetitive manner. This review discusses the use of phage with adjuvanting activity as antigen delivery vehicles for vaccination against infectious disease and cancer. K E Y W O R D S bacteriophage, biomaterials, drug delivery, immunology, nanotechnology, phage display, vaccine 1 | INTRODUCTION Bacteriophages, or phages, are prokaryotic viruses that specifically infect bacteria, and are the most abundant life form on earth. 1 Phages were first discovered in the early 20th century and noted for their antibacterial activity. The practice of administering phages (i.e., phage therapy) to patients suffering from bacterial infections began shortly after their discovery, but was controversial largely due to lack of mechanistic knowledge and variable success rates. In fact, the treatment was largely abandoned upon the discovery of antibiotics. 2 Research in this field was reenergized, however, following the development of phage display systems in 1985. 3 George Smith, a chemist at the University of Missouri, demonstrated fusion of peptides to the outer (i.e., capsid) proteins of phages enabling surface display. This work, for which Smith shared a Nobel Prize in 2018, laid the ground work for affinity selection, epitope mapping, and antibody discovery. Since this time, phages have been an important tool for the bioengineering field, exploited for a range of applications including theranostics, 4 batteries, 5,6 drug delivery, 7 and vaccine development. 1Phages are one of many nanotechnologies being investigated for these applications. This review will focus on the advantages that phages provide to the nanomedicine field, specifically vaccination and immunotherapy. Nanomedicine ranges from diagnostics to treatments and relies on the fields of biomedical and chemical engineering,

Phage Display Technique as a Tool for Diagnosis and Antibody Selection for Coronaviruses

“…The technique has many applications, such as selection of monoclonal antibody and bioactive peptides, epitope mapping, selection of disease specific antigen mimics, cell-specific or organ-specific peptides, peptidomimetics and development of drug delivery systems [ 6 – 9 ]. Thus, phage display has been widely used in immunotherapy, regenerative medicine, development of biosensors and synthetic biology [ 5 , 10 – 13 ].…”

Bacteriophage-Based Vaccines: A Potent Approach for Antigen Delivery

“…As mentioned in previous sections, phage display has been proposed as a potent tool for vaccine development [ 51 , 52 ]. This technology has been used for this purpose in two main strategies: (1) to produce vectors displaying antigens and (2) to identify new protective antigens [ 6 ].…”

Perspectives in Peptide-Based Vaccination Strategies for Syndrome Coronavirus 2 Pandemic

“…The advantages of VLPs include similar size and antigenicity of the corresponding viruses and lack of viral genome and, as consequence, of danger. A VLP modification is constituted by VLPs assembled from the coat protein of bacteriophages ( Bao et al, 2019 ; Manoutcharian, 2005 ; Hess and Jewell, 2020 ). In liposomes, antigen can be entrapped inside them (soluble antigens) or incorporated into lipophilic bilayer (lipophilic antigens) ( Figure 2B ) ( De Serrano and Burkhart, 2017 ).…”