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Review
.2019 Sep 1;11(9):437.
doi: 10.3390/pharmaceutics11090437.

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

Affiliations
Review

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

Rossella Sartorius et al. Pharmaceutics..

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.

Keywords: antigen delivery; filamentous bacteriophage; nanoparticle; phage display; targeting; vaccine.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic image of a filamentous bacteriophage nanoparticle engineered for the expression of a short antigenic peptide as a fusion with N-terminus of the pVIII protein and a single-chain antibody fragment (scFv) for the targeting, as a fusion with the N-terminus of the pIII protein. The circular single-strand DNA rich in CpG motifs can be recognized by PPR and acts as an adjuvant.
Figure 2
Figure 2
Filamentous bacteriophage nanovaccine can stimulate the humoral response or be taken up by antigen-presenting cells (APCs). The displayed antigenic peptides are processed and presented on MHCI and II molecules, leading to a CD4 and CD8 immune response. The presence of CpG sequences into the phage genome drives to APC maturation. GC (Germinal Center); FDC (Follicular Dendritic Cell). The figure depicts the possible scenario of target mediated fd internalization based on scientific results reported in [39,49].
Figure 3
Figure 3
Once internalized via the DEC205 endocytic receptor, the filamentous bacteriophage is directed to the late endosomal compartments. Here the bacteriophage coat is degraded, and the CpG-rich DNA sequence starts the Toll-like receptor 9 (TLR9) mediated immune response with the activation of several transcription factors. A possible mechanism of endosomal escape is depicted and indicated with a question mark. Partially degraded viral DNA translocated to the cytosol starts a STING-mediated transcription activation. Type I IFNs promotes the STAT1/STAT2/IRF9 association to form the ISGF3 transcription factor regulating the transcription of IFN-stimulated genes (ISGs); IFNAR (Interferon-alpha/beta receptor). The figure depicts the possible scenario of target mediated fd internalization based on scientific results reported in [64,78].
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