Arming Filamentous Bacteriophage, a Nature-Made Nanoparticle, for New Vaccine and Immunotherapeutic Strategies

Abstract

The pharmaceutical use of bacteriophages as safe and inexpensive therapeutic tools is collecting renewed interest. The use of lytic phages to fight antibiotic-resistant bacterial strains is pursued in academic and industrial projects and is the object of several clinical trials. On the other hand, filamentous bacteriophages used for the phage display technology can also have diagnostic and therapeutic applications. Filamentous bacteriophages are nature-made nanoparticles useful for their size, the capability to enter blood vessels, and the capacity of high-density antigen expression. In the last decades, our laboratory focused its efforts in the study of antigen delivery strategies based on the filamentous bacteriophage ‘fd’, able to trigger all arms of the immune response, with particular emphasis on the ability of the MHC class I restricted antigenic determinants displayed on phages to induce strong and protective cytotoxic responses. We showed that fd bacteriophages, engineered to target mouse dendritic cells (DCs), activate innate and adaptive responses without the need of exogenous adjuvants, and more recently, we described the display of immunologically active lipids. In this review, we will provide an overview of the reported applications of the bacteriophage carriers and describe the advantages of exploiting this technology for delivery strategies.

Investigation of intestinal transportation of peptide‐displaying bacteriophage particles using phage display method

“…For instance, the phage particles were used as nanocarriers in drug delivery, [43][44][45][46][47][48] gene delivery, [49][50][51][52][53] and antigen delivery system in vaccination. 54,55 Taken together, the findings in this investigation indicated that Note: The mean hydrophobicity values and the corresponding standard deviation (SD) are shown for the residues observed in different positions (I-XII) of the displayed peptides at the N-terminus of pIII coat protein for total isolated phages. The statistical analysis of the results demonstrated that the calculated mean hydrophobicity for the each position of peptide sequences is not significantly different from each other (p value > 0.05).…”

“…The broad application of phage for delivery purposes have been also documented by several studies. For instance, the phage particles were used as nanocarriers in drug delivery, 43–48 gene delivery, 49–53 and antigen delivery system in vaccination 54,55 …”

Bacteriophages as Therapeutic and Diagnostic Vehicles in Cancer

“…Filamentous bacteriophages such as M13 are capable of inducing immunity at different levels, as excellently discussed in reviews by De Berardinis’ group [ 68 , 69 ] and others [ 70 ]. Being particulate, they are uptaken and processed by antigen processing cells (APCs), followed by presentation of the deriving peptides by the major histocompatibility complex (MHC) class I and class II molecules.…”

Analysis of the Consolidation Phase of Immunological Memory within the IgG Response to a B Cell Epitope Displayed on a Filamentous Bacteriophage

“…Filamentous bacteriophage fd has been proposed as an antigen delivery system for vaccination against tumors, parasites, viruses, and neurodegenerative diseases [11,12,[25][26][27]. Our results suggest that the design of B epitope-specific immunization protocols based on phage fd should take into account the interindividual variability in the strength of the secondary IgG response and the possible disruptive effect of a day 15 booster dose on immunological memory.…”