Phage display as a promising approach for vaccine development

Abstract

Bacteriophages are specific antagonists to bacterial hosts. These viral entities have attracted growing interest as optimal vaccine delivery vehicles. Phages are well-matched for vaccine design due to being highly stable under harsh environmental conditions, simple and inexpensive large scale production, and potent adjuvant capacities. Phage vaccines have efficient immunostimulatory effects and present a high safety profile because these viruses have made a constant relationship with the mammalian body during a long-standing evolutionary period. The birth of phage display technology has been a turning point in the development of phage-based vaccines. Phage display vaccines are made by expressing multiple copies of an antigen on the surface of immunogenic phage particles, thereby eliciting a powerful and effective immune response. Also, the ability to produce combinatorial peptide libraries with a highly diverse pool of randomized ligands has transformed phage display into a straightforward, versatile and high throughput screening methodology for the identification of potential vaccine candidates against different diseases in particular microbial infections. These libraries can be conveniently screened through an affinity selection-based strategy called biopanning against a wide variety of targets for the selection of mimotopes with high antigenicity and immunogenicity. Also, they can be panned against the antiserum of convalescent individuals to recognize novel peptidomimetics of pathogen-related epitopes. Phage display has represented enormous promise for finding new strategies of vaccine discovery and production and current breakthroughs promise a brilliant future for the development of different phage-based vaccine platforms.

Keywords: Bacteriophage; Biopanning; Mimotope; Peptide library; Phage display; Vaccine development.

Fig. 1

Schematic representation of phage display Cloning of foreign DNA into the gene which encodes one of the phage coat proteins leads to the expression of guest amino acid sequence as part of the relevant coat protein on the phage surface. In phage display, the displayed peptide (phenotype) and its encoding nucleotide sequence (genotype) are physically linked together in an individual phage particle

Fig. 2

Biopanning for the identification of target-specific phage-displayed peptides The incubation of a randomized peptide phage display library with the target is followed sequentially by multiple washing steps (to remove the unbound phages), recovery of target-bound phages, and their amplification through bacterial infection. These steps are repeated 3–5 rounds. Finally, selected phage clones displaying peptides with the highest affinity towards the target are identified through DNA sequencing

Fig. 3

Phage DNA vs. phage display vaccine a) In phage DNA vaccine, a eukaryotic gene expression cassette containing the antigen sequence is cloned into the phage genome. Therefore, the antigen expression is under the control of eukaryote-derived regulatory sequences. b In phage display vaccine as the main phage-based strategy for vaccine design, the vaccine sequence is cloned into the phage coat protein gene. Therefore, the antigenic amino acids are expressed as fusion to the coat protein on the phage surface. These antigenic amino acid residues are readily presented to the immune system