IgY antibodies for the immunoprophylaxis and therapy of respiratory infections

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

Pseudomonas aeruginosa in patients with cystic fibrosis (CF) CF is a multisystem autosomal recessive disorder affecting approximately 70,000 people worldwide. 96 CF is caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This CFTR dysfunction results in very thick secretions in the airways, leading to difficult mucociliary clearance. 96 Pseudomonas aeruginosa is very common in CF patient, resulting in a decline in lung function with higher morbidity and mortality. 97, 98 Eradication of P. aeruginosa is difficult and patients usually experience chronic infection. 4, 99 A characteristic change in the bacteria during the course of infection is alginate production, which leads to greater difficulty in pathogen eradication. 4, 99 Antibiotic therapy is currently the best management approach in these cases. 100 Early interventions targeting the bacterial colonization step can prevent the chronic stage from developing, 66 while later interventions that fail to eradicate P. aeruginosa in CF patients will increase the risk of exacerbation. 101 Binding of IgY to P. aeruginosa early in the course of infection prevents adhesion of the bacteria to oropharynx, which can prevent bacterial colonization. 102 IgA in the In vitro Purified IgY preparations, obtained from hens immunized with BRSV, neutralized BRSV in vitro respiratory mucosa appears to have a role in the initial host response by helping to reduce bacterial colonization. 103 Consequently, CF patients with IgA deficiency could have greater susceptibility to bacterial colonization. 104 Passive immunization with IgY could prophylactically augment mucosal IgA immunity, thus increasing the resistance to P. aeruginosa colonization. 105 IgY was found to induce rapid and competent bacterial clearance in a murine pneumonia model. 18 This study found that the pulmonary bacterial load in anti-P. aeruginosa IgYtreated mice was lower than in the controls by more than 2log after 24 hours of infection. The IgY was found to induce a rapid decline in the bacterial load within the first hours of infection. The IgY-treated mice had a better clinical state compared to controls, which may be attributable to a lack of disseminated infection since anti-P. aeruginosa IgY protected against bacteremia. 18 Production of inflammatory cytokines accompanied the faster bacterial clearance in treated mice. IL-1β and TNF-α, potent mediators of inflammation, were significantly reduced in anti-P. aeruginosa IgY-treated mice compared to controls after 24 hours of infection. Accordingly, the PMN mobilizer granulocyte-colony stimulating factor (G-CSF) and the PMN chemoattractant and murine IL-8 analog macrophage inflammatory protein-2 were significantly decreased at 24 hours post infection in the anti-P. aeruginosa IgY-treated group compared to controls, suggesting a moderation of neutropoiesis consistent with reduced numbers of the bacteria. Lung pathology caused by P. aeruginosa was reduced by the antibacterial activity of IgY immunotherapy (Table 1) . 18 The prophylactic effects of intranasal administration of IgY antibodies were more notable than intranasal spray 6 hours post infection. The superiority of the prophylactic treatment could have been due to the presence of IgY antibodies in the airways, which prepared the mucosal surface for the opsonophagocytic process and reduced its interaction with the IgY opsonized pathogens. 105 Anti-Pseudomonas IgY was shown to bind the P. aerug