Z. Peng

Novel cytokine peptide‐based vaccines: an interleukin‐4 vaccine suppresses airway allergic responses in mice

Background:  Monoclonal antibodies or soluble receptors have been used to block over‐produced endogenous cytokines. However, they have disadvantages of short half‐lives, high costs, and possible adverse effects. Using interleukin (IL)‐4 as a model target, we sought to develop a novel therapeutic strategy by constructing an IL‐4 peptide‐based vaccine for blocking IL‐4 on a persistent basis, and to evaluate its efficacy in a mouse model of asthma.

Targeting IL-23 by employing a p40 peptide-based vaccine ameliorates murine allergic skin and airway inflammation

Studies have found that the IL‐23/Th17 pathway plays an important role in the pathogenesis of atopic dermatitis (AD) and severe and steroid‐resistant asthma. Targeting IL‐23/Th17 pathway with monoclonal antibodies (mAb) has been successful in the reduction of skin and airway inflammation in animal models. However, the mAb has a short half‐life, requiring repeated administrations. For the long‐term suppression of IL‐23/Th17 pathway, we have previously developed an IL‐23p40 peptide‐based virus‐like particle vaccine, which induces long‐lasting autoantibodies to IL‐23.

Virus-like particles presenting interleukin-33 molecules: Immunization characteristics and potentials of blocking IL-33/ST2 pathway in allergic airway inflammation

We sought to develop an IL-33 vaccine and evaluate its efficacy in a mouse model of asthma. The full-length molecules of putative mature IL-33 were inserted into the immunodominant epitope region of hepatitis B core antigen using gene recombination techniques. The expressed chimeric protein presented as virus-like particles (VLPs) under observation using an electron microscopy. To investigate immunization characteristics of the VLPs, mice were immunized by using different doses, adjuvants, and routes. The VLPs induced sustained and high titers of IL-33-specific IgG and IgA even without the use of a conventional adjuvant, and the lowered ratio of IgG1/IgG2a in vaccinated mice indicated a shift from Th2 to Th1-like responses. To assess the vaccine effects on blocking the signaling of IL-33/ST2 pathway, mice receiving 3 vaccinations subjected to intraperitoneal sensitization and intranasal challenge with ovalbumin (OVA). Control animals received carrier or PBS in place of the vaccine. Immunization with the VLPs significantly suppressed inflammatory cell number and IL-33 level in BALF. OVA -induced goblet cell hyperplasia and lung tissue inflammatory cell infiltration were significantly suppressed in vaccinated mice. Our data indicate that IL-33 molecule-based vaccine, which may block IL-33/ST2 signaling pathway on a persistent basis, holds potential for treatment of asthma and, by extension, other diseases where overexpressed IL-33 plays a pivotal role in pathogenesis.

Immunization against TGF-β1 reduces collagen deposition but increases sustained inflammation in a murine asthma model

ABSTRACT Transforming growth factor (TGF)-β1 is involved in the processes of airway inflammation and remodeling; however, its reported roles in asthma pathogenesis are controversial. We sought both to investigate the effects of active immunization targeting TGF-β1 on allergen-induced airway inflammatory responses and to evaluate its possible application for asthma treatment. BALB/c mice were immunized with a virus-like-particle (VLP) vaccine presenting a TGF-β1 peptide. For the preventive intervention of acute allergic airway inflammation, immunization was conducted before sensitization and challenges with ovalbumin (OVA), and for the therapeutic treatment of chronic inflammatory responses, immunization was initiated after inflammatory responses were established. Preventive immunization with VLPs led to increased proinflammatory IL-4, IL-13, and IL-33 levels in the bronchoalveolar lavage fluids (BALF) with no significant effects on lung tissue inflammation and airway goblet cell hyperplasia. Therapeutic treatment showed that at 24 h after the fourth 2-day challenge with OVA following 2 intraperitoneal sensitizations, airway subepithelial collagen deposition was significantly ameliorated in vaccinated mice, whereas the lung histology and cytokine profile in the BALF were not changed. In contrast, after a 4-week recovery from the last OVA challenge, the vaccinated mices collagen deposition remained reduced, but they sustained lung-tissue inflammation and goblet-cell hyperplasia; elevated IL-13, TNF, and IFN-γ levels in the BALF; and increased airway resistance, tissue resistance, and tissue elastance. In a conclusion, the role of TGF-β1 is complicated in allergic airway inflammatory responses. It is important to make a careful assessment in accordance with specific disease conditions when targeting TGF-β1 for a therapeutic purpose.