Amongst them, IL-5 is responsible
for the selective differentiation of eosinophils [7]. IL-5 also stimulates release of eosinophils from the bone marrow into the peripheral circulation and promotes their migration to the lung upon allergen challenge; a key step in the development of lung inflammation [8] and [9]. In accord with these important roles for IL-5, antibodies that Screening Library in vitro neutralize IL-5 inhibit both allergen-induced blood eosinophilia and the recruitment of eosinophils to the lung in murine models of asthma [10] and [11]. In addition to IL-5, cytokines from the eotaxin family also stimulate eosinophils to migrate from blood into tissues [12]. There are two variants of murine eotaxin, namely eotaxin 1 (eotaxin) and eotaxin 2 which both belong to the family of CC type chemokines [13] and [14]. Murine eotaxin has marked synergism with IL-5. Anti-eotaxin and anti-IL-5 antibodies alone and in combination have been shown click here to reduce OVA-induced airway eosinophilia but failed to inhibit AHR [15]. Importantly, blocking eosinophil-activity in mice prevents allergen induced airway eosinophilia and AHR and results in reduced lung-fibrosis, a severe consequence of asthma [16] and [17]. For humans, therapeutic intervention strategies aimed at blocking the action of eosinophils have been investigated in various asthma settings and eosinophilic disorders. Blockade of IL-5
with the humanized monoclonal antibody Mepolizumab has reduced circulating and
sputum eosinophils and shown evidence for an effect on airway remodelling [17] but, has failed to achieve discernable effects on AHR or the late asthmatic response. Recent clinical testing of Mepolizumab in refractory eosinophilic asthma and prednisone dependent asthma has shown decreases in blood and sputum eosinophils and statistically significant decreases in the number of asthma exacerbations Bay 11-7085 [18] and [19]. Thus, anti-eosinophil strategies may be a promising therapy in asthma subgroups with heavy eosinophilic loads in which conventional anti-inflammatory therapy is only partially effective. Monoclonal antibodies (mAbs) are highly active molecules that are currently used in a numerous disease indications, including cancer and inflammation. However, due to the high amounts of antibodies required and their generally short half-life, therapies involving monoclonal antibodies are costly. In addition, long-term treatment with mAbs may result in the development of neutralizing anti-antibodies, which may reduce their efficacy or induce adverse effects [20]. Active immunization against self-antigens typically results in relatively long-lived antibody responses and has been viewed as a potential alternative to mAb therapies. It has previously been shown that highly repetitive antigens displayed on viral surfaces are able to efficiently overcome B cell unresponsiveness [21].