Beyond phage display: non-traditional applications of the filamentous bacteriophage as a vaccine carrier, therapeutic biologic, and bioconjugation scaffold

Abstract

For the past 25 years, phage display technology has been an invaluable tool for studies of protein–protein interactions. However, the inherent biological, biochemical, and biophysical properties of filamentous bacteriophage, as well as the ease of its genetic manipulation, also make it an attractive platform outside the traditional phage display canon. This review will focus on the unique properties of the filamentous bacteriophage and highlight its diverse applications in current research. Particular emphases are placed on: (i) the advantages of the phage as a vaccine carrier, including its high immunogenicity, relative antigenic simplicity and ability to activate a range of immune responses, (ii) the phage’s potential as a prophylactic and therapeutic agent for infectious and chronic diseases, (iii) the regularity of the virion major coat protein lattice, which enables a variety of bioconjugation and surface chemistry applications, particularly in nanomaterials, and (iv) the phage’s large population sizes and fast generation times, which make it an excellent model system for directed protein evolution. Despite their ubiquity in the biosphere, metagenomics work is just beginning to explore the ecology of filamentous and non-filamentous phage, and their role in the evolution of bacterial populations. Thus, the filamentous phage represents a robust, inexpensive, and versatile microorganism whose bioengineering applications continue to expand in new directions, although its limitations in some spheres impose obstacles to its widespread adoption and use.

Bacteriophages and phage-inspired nanocarriers for targeted delivery of therapeutic cargos

“…Modifications to the peptides also can be carried out by using enzymes, when the displayed peptide contains a domain subject to enzymatic conversion[27]. Among different types of phage, the filamentous phages particularly M13, are the main platform used in display libraries[28]. T4, T7 and lambda phages have also been used to a lesser extent as alternative vectors to construct display libraries.…”

“…To this end, a more effective purification system is required, and the amount of LPS could be diminished in the final product by using size exclusion columns combined with polymyxin B binding chromatography, and finally treating with a detergent like Triton. Secondly, the use of phages might be restricted in high-risk patients owing to their immune status and the heterogeneity of the particles[28]. …”

“…The monodispersity of the phage coat protein would be an ideal advantage for hybrid preparation via the phage self-assembly process. Filamentous phages with their rod-shaped structure have been extensively studied as a liquid crystal model system; factors such as the ionic strength of the solution, the concentration of phages, and application of external force have encouraged the formation the liquid crystal phase[28, 128, 129]. The introduction of inorganic materials onto the surface of phages displaying ligands, imparts novel properties to the phage carriers.…”

The development of inovirus-associated vector vaccines using phage-display technologies

“…While viruses have often been considered pernicious as they co-opt a host for their own survival, often killing the host in the process, new work with viruses that can be exploited as bacteriophages but without the harmful effects has arisen [3]. These viruses, which can be easily manipulated and employed for phage display ability, are being increasingly used for a variety of potent biomedical tools [4]. These filamentous bacterial viruses, which make up the genus Inovirus in the family Inoviridae, are thread-like viruses containing single-stranded DNA genomes know as filamentous bacteriophages [5][6][7].…”

PhiXing-it, displaying foreign peptides on bacteriophage ΦX174

“…Numerous systems based on bacteriophages T4, T7, λ, MS2, PP7, Qβ, and filamentous phage have been developed for diverse applications, which include the selection of peptide or protein binders through phage display, the development of novel imaging reagents, biosensors, bio-nanoconjugate applications, and for antigen display platforms for serological assays, epitope mapping, and vaccine development (Henry et al, 2015; Lee et al, 2013; Levy et al, 2007; O’Rourke et al, 2015; Seker and Demir, 2011). Peptide display from viral capsid or virus-like particle (VLP) scaffolds is empirical by nature; it is impossible to predict whether a given peptide will be tolerated or will perform successfully in any given application.…”