IgY antibodies for the immunoprophylaxis and therapy of respiratory infections

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

Respiratory tract infections (RTIs) represent one of the most common illnesses encountered in clinical medicine. In developed countries, RTIs account for the majority of antibiotic prescriptions, more than 30% of lost work-days, and 20% of all medical consultations. 1 About 1.3 million children under 5 years die from acute respiratory infections (ARI) worldwide every year 2 and represents the cause of death in one third of children under five years in developing countries. 3 Multidrug-resistant (MDR) or difficult-to-treat pathogens are an enormous challenge to the global health care community because of the high morbidity and mortality associated with them as well as the economic burden that they place on patients and the health care system. Antibiotics are a major tool in managing infections caused by these pathogens, [4] [5] [6] [7] [8] but the emergence of antibiotic resistance has undermined their usefulness in some cases. Furthermore, a substantial proportion of respiratory infections are acute viral infections. The management of such infections includes use of antivirals and treatment to relieve disease symptoms. However, most antiviral agents target conserved viral proteins, which places selective pressure on the virus, leading to the development of antiviral resistance. 9 Viral infections can be prevented by vaccination, but vaccine development faces multiple challenges, including antigenic variations in viral strains, low efficacy or short-term immune responses. In the case of outbreaks, rapid vaccine development may not be possible to control the spread of infection. 10 Therefore, an urgent need exists to develop novel approaches to treat and manage the respiratory infections Passive immunization offers an alternative approach for treating infections in immune-compromised individuals and avoiding any side effects that might result from vaccination. 11 Antibody preparations used for passive immunization mainly contain polyclonal antibodies derived from the sera of immunized animals, immunized humans, and in some cases convalescing patients. 12, 13 The effective use of polyclonal antibodies faces several challenges, including standardization and patient safety. Monoclonal antibodies (mAbs) have been suggested as an alternative to polyclonal antibodies, but their use is limited by high production cost (about US$100/g). 14 In addition, the possibility of viral escape mutants requires production of numerous mAbs targeting several antigens. This strategy would increase the cost and require additional efficacy and safety studies. 15 Immunoglobulin (Ig)Ys are produced by chickens and other birds, reptiles, and amphibians. The function of IgYs is similar to that of mammalian IgGs. 16 IgYs are present in the sera of chickens and are passed to the embryo through egg yolk. 17 Egg IgY antibodies have previously been used against bacterial 18 and viral infections. 19 IgY is well tolerated because chicken eggs are a natural part of the human diet. In addition, it can be used in patients with egg allergies because the purified IgY does not contain egg albumin, the common trigger for allergic reactions to eggs. 20 Moreover, the immunogenicity of IgY has been tested previously in both pigs and mice. Vega et al 21 and Torche et al 22 have both demonstrated that administration of IgY to pigs via both systemic and local routes induced an anti-IgY antibody response, primarily consisting of the IgG subclass. These data suggest that IgY is antigenic