**1. Introduction: Why Develop an Anti-IL-13 Vaccine?**

In an age dominated by an avalanche of monoclonal antibodies (MAb) hitting the market for a dizzying variety of conditions, one may ask why replacing this obvious successful model with a vaccine strategy is sensible at all. The answer to this question is four-fold. Two of these are generic and would apply to many vaccines replacing a MAb treatment. First, it will be much more accessible to patients (economics). Second, it will have much broader applications thanks to the qualitatively different nature of a polyclonal vs. a monoclonal immune response (see below for details). The third reason is more limited to IL-13: it has an excellent safety profile as a target compared to almost all other cytokines, with the exception of IL-17. Fourth, and finally, very recent data suggest that targeting IL-13 with a VLP vaccine may have very broad anti-allergic potential, possibly leading to amelioration of allergies and being able to achieve synergistic effects with other anti-allergic treatments. The present review will discuss these four themes in turn, not aiming to be exhaustive, but rather with the intent to stimulate further efforts to tackle many open questions. By implication, therefore, this review does not intend to deliver a broader review of the signalling, structure, or immunobiology of IL-13 which have been reviewed excellently recently elsewhere [1–3].

#### **2. Virus-Like Particles as a Construct for IL-13 Therapeutic Vaccine**

Virus-like particle (VLP) vaccines are nanostructures generated by self-assembly of structural proteins resembling the native version in their morphology and composition but lack the genomic material of infectious capacity [4,5]. VLPs can be acquired from a variety of expression systems and platforms including bacteriophages (MS2, PP7 and AP205 [6–8]), yeast (*Hansenula polymorpha* and *Saccharomyces cerevisiae* [9,10]), bacteria (*Escherichia coli* [8]), mammalian cell lines (Vero, 293T and BHK cell lines [11–13]), plant cell culture (cowpea mosaic virus, cucumber mosaic virus, tobacco mosaic virus, and bean yellow dwarf virus [14–16]) and insect cell lines (Baculovirus and Sf9 cell line [12,17]) [18]. Vaccine development faces a clear challenge: production of sufficient amounts of quality antibodies to target the desired antigen. VLPs provide an excellent vaccine delivery platform due to their composition: their small size (usually 20–200 nm), geometry and flexibility during development [4]. Their size allows easy passage and drainage through the lymph to reach all areas such as secondary lymphoid organs resulting in profound effects in targeting follicular B cells [4,19–21]. Furthermore, CD8+ and plasmacytoid subsets of dendritic cells (DCs) can cross-present small-sized antigens such as VLPs and active B cells and T cells in the lymph nodes to induce cytotoxic effects [20,22,23]. Repetitive multivalent surface arrangement allows cross-linking of B cell receptors, perfect for inducing great amounts and long-lasting antibodies [20,24]. VLPs also act as a template for further engineering, where additional epitopes, proteins and nucleic acids are easily incorporated alongside vaccine targets that can significantly increase immunity such as Toll-like receptor (Tlr) ligands [20,25]. These characteristics can thus provide solutions for vaccine delivery challenges and are readily modified for a vast variety of constructs to boost immune responses in many individuals.
