IgY antibodies for the immunoprophylaxis and therapy of respiratory infections

Abbas, Aymn Talat; El-Kafrawy, Sherif Aly; Sohrab, Sayed Sartaj; Azhar, Esam Ibraheem Ahmed

One of the most useful characteristics of IgYs is their stability during processing steps and under physiological conditions after administration. 24 IgYs were found to be stable during storage at room temperature or at 4°C for 6 months without losing their activity. 76 Furthermore, IgY antibodies can be stored for 5-10 years at 4°C without significant loss of their activity; they can even retain their activity after storage for 6 months at room temperature or for 1 month at 37°C. 77 IgYs are preferably stored at −20°C for long-term storage; storage at −70°C can cause up to 50% loss of their activity. 78 The stability of IgY is not affected by freeze-drying, although repeated freeze-thaw cycles might compromise its activity. 79 One report 80 showed that the thermal stability of IgYs was not affected by lyophilization at 90°C for 15 minutes. Long-term storage of IgY is better achieved by spray drying to avoid losing antibody potency. 81 Acid stability of IgY antibodies is reported to be between pH 4 and 11, while activity decreases at lower pH values. 75, [82] [83] [84] [85] The loss of activity at lower pH values might be due to conformational changes that distort the antigen-binding site. 75, 84 IgY antibodies are stable in alkaline conditions up to pH 11.0, while they lose activity at pH values ≥ 12. 75, 82 Safety Safety is a major way in which IgY is superior to mammalian IgG. IgYs are safer than IgGs because they do not bind to human Fc receptors or fix mammalian complement components, hence they do not trigger potentially dangerous immune responses. 17 Kubickova et al 86 exposed immortalized human lung epithelial cells to IgY, using lipopolysaccharide as a positive control and phosphate-buffered saline as a negative control. Treatments also included exposure to human and goat IgG, and exposure lasted 24 hours for all treatments. The researchers found that the levels of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were very low in cell cultures treated with IgY compared with the high levels of TNF-α and GM-CSF in cells treated with lipopolysaccharides, indicating that IgYs do not cause inflammatory responses in lung cells and can thus be safely used for prevention of airway infections. 86 Additionally, oral IgY antibodies have been applied to treat rotavirus infections in humans 54 and to treat pulmonary Pseudomonas aeruginosa infections, and no negative side effects of IgY treatment have been observed in up to 10 years of use. 87 The safety of intranasal IgY delivery has been documented for the treatment of influenza virus 19 and acute and chronic pharyngitis for human. 88 Use of IgY for the treatment of respiratory infections Influenza Worldwide, influenza viruses cause 3-5 million hospitalizations and 250,000-500,000 deaths annually. 89, 90 Vaccination and antiviral drugs are the current approaches for the prevention and treatment for this infection. 91 The long time needed to prepare a new influenza vaccine (about 6 months) for the new strains leave the population vulnerable to infection. 92 The available antiviral drugs have limited efficacy because the virus can develop resistant variants with different active target binding sites. Consequently, the drugs are not effective when taken beyond the third day of infection. 93 The rapid development of new treatments against influenza is a critical need that would intensify in a pand