Therapeutic and prophylactic applications of bacteriophage components in modern medicine

Abstract

As the interactions of phage with mammalian innate and adaptive immune systems are better delineated and with our ability to recognize and eliminate toxins and other potentially harmful phage gene products, the potential of phage therapies is now being realized. Early efforts to use phage therapeutically were hampered by inadequate phage purification and limited knowledge of phage-bacterial and phage-human relations. However, although use of phage as an antibacterial therapy in countries that require controlled clinical studies has been hampered by the high costs of patient trials, their use as vaccines and the use of phage components such as lysolytic enzymes or lysozymes has progressed to the point of commercial applications. Recent studies concerning the intimate associations between mammalian hosts and bacterial and phage microbiomes should hasten this progress.

Figures

Figure 1.

Immune activation of mammalian system with phage display antigens. (1) Particulate nature of phage activates the antigen-presenting cells (APC), which process the antigens for immune presentation. (2) Presentation of processed antigens by major histocompatibility complexes (MHC) class I molecules to CD8 T cells, which leads to T-cell activation. (3) Antigens are presented by MHC class II molecules to CD4 T cell, which in turn activates Th1 and Th2 effector cells. (4) Th1 cells generate cytotoxic T-cell (CTL) responses and help produce interferon γ (IFN-γ). (5) Th2 cells activate B cells to make antibodies. (6) Direct activation of B cells by phage vaccines also leads to massive antibody response. T-cell receptors are denoted by TCR.

Figure 2.

Schematic representations of several phage-mediated vaccine delivery systems. (1) Production of virus-like particles (VLPs) by adding purified phage capsid proteins fused to antigens during assembly of phage particles in vitro. (2) Antigens are attached by chemical conjugation on preassembled phage head. (3) Antigens are displayed on phage surface by fusion of antigen genes with phage capsid protein genes. (4) Phage as a DNA delivery vehicle where antigen genes are cloned in phage genome under the control of eukaryotic promoters. (5) Phage for DNA vaccine, where phage carries antigen genes under the control of eukaryotic promoters. The phage also displays foreign proteins on its surface as fusion of phage capsid proteins. This protein targets the phage to antigen-presenting cells (APC).