Avian Egg Yolk Antibodies (IgY) and their Potential Therapeutic Applications...

[Full title: Avian Egg Yolk Antibodies (IgY) and their Potential Therapeutic Applications for Countering Infectious Diseases of Fish and Aquatic Animals]

OPEN ACCESS International Journal of Pharmacology ISSN 1811-7775 DOI: 10.3923/ijp.2016.760.768 Review Article Avian Egg Yolk Antibodies (IgY) and their Potential Therapeutic Applications for Countering Infectious Diseases of Fish and Aquatic Animals 1 Mohammad Jalil Zorriehzahra, 2 Ruchi Tiwari, 3 Swati Sachan, 4 Kumaragurubaran Karthik, 5 Yashpal Singh Malik, 6 Maryam Dadar, 7 Muhammad Sarwar, 8 Maryam Sayab and 9 Kuldeep Dhama 1 Department of Aquatic Animal Health and Diseases, Iranian Fisheries Science Research Institute (IFSRI), Agricultural Research Education and Extension Organization (AREEO), Tehran, Islamic Republic of Iran 2 Department of Veterinary Microbiology, College of Veterinary Science and Animal Husbandry, Uttar Pradesh Pandit Deen Dayal Upadhayay Pashu Chikitsa Vigyan Vishwa Vidyalaya Evam Go-Anusandhan Sansthan (DUVASU), 281001 Mathura, Uttar Pradesh, India 3 Immunology Section, ICAR-Indian Veterinary Research Institute (IVRI), 243122 Izatnagar, Uttar Pradesh, India 4 Division of Bacteriology and Mycology, ICAR-Indian Veterinary Research Institute (IVRI), 243122 Izatnagar, Uttar Pradesh, India 5 Division of Biological Standardization, ICAR-Indian Veterinary Research Institute (IVRI), 243122 Izatnagar, Uttar Pradesh, India 6 Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran 7 G.M. College for Science and Technology, Faisalabad, Pakistan 8 ACE College for Women, Sargodha Road, Faisalabad, Pakistan 9 Division of Pathology, ICAR-Indian Veterinary Research Institute (IVRI), 243122 Izatnagar, Uttar Pradesh, India Abstract In the current scenario of increasing and emerging drug resistance in various microbial pathogens, traditional antibiotics are becoming less effective and thus globally research has focused on developing alternative therapeutic regimens having efficient germ killing abilities. The leading alternatives include use of phages, prebiotics, probiotics, cytokines, avian egg yolk antibodies, toll like receptors, medical herbs and various other immunomodulatory/immunotherapeutic approaches. Out of these valuable therapies, the application of oral passive immunization using avian egg yolk antibodies (Immunoglobulin Y, IgY) offers promising future avenues for designing and developing novel prophylactic and treatment strategies against infectious diseases in both humans and animals, particularly countering the enteric pathogens. Hitherto studies confirm beneficial applications of IgY antibodies in animals (Calves, lamb and goat, cats and dogs), poultry and humans, however such studies in fish and aquatic animals are comparatively less. The present study presents as overview on avian egg antibodies, their salient features, advantages and limitations and then describes the potential therapeutic applications of IgY for the prevention and treatment of infectious diseases of fish and aquatic animal species, as well as speculating the future prospects of upcoming IgY technology. Taking into account the valuable prophylactic and therapeutic applications of IgY antibodies, further explorative research in this area could pave way for designing and developing effective pharmaceuticals and treatment options for various infectious diseases of fish/aquaculture animals as well as for safeguarding health of humans and their companion animals Key words: Avian egg antibodies, IgY, egg yolk, fish, aquatic animals, infectious diseases, prophylaxis, therapy Received: July 28, 2016 Accepted: September 09, 2016 Published: October 15, 2016 Citation: Mohammad Jalil Zorriehzahra, Ruchi Tiwari, Swati Sachan, Kumaragurubaran Karthik, Yashpal Singh Malik, Maryam Dadar, Muhammad Sarwar, Maryam Sayab and Kuldeep Dhama, 2016. Avian egg yolk antibodies (IgY) and their potential therapeutic applications for countering infectious diseases of fish and aquatic animals. Int. J. Pharmacol., 12: 760-768 Corresponding Author: Kuldeep Dhama, Division of Pathology, ICAR-Indian Veterinary Research Institute (IVRI), 243122 Izatnagar, Uttar Pradesh, India Copyright: © 2016 Mohammad Jalil Zorriehzahra et al . This is an open access article distributed under the terms of the creative commons attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited. Competing Interest: The authors have declared that no competing interest exists Data Availability: All relevant data are within the paper and its supporting information files.

Int. J. Pharmacol., 12 (8): 760-768, 2016 INTRODUCTION The emergence of drug resistant microbial pathogens is prompting scientists to search for other germ-killing option like the use of alternative and complementary therapeutic regimens like phages, prebiotics, probiotics, cytokines, avian egg yolk antibodies, toll like receptors, medical herbs and various immunomodulatory/immunotherapeutic approaches to counter infectious diseases of aquatic animals 1-7 . Out of these, avian egg yolk antibodies (EYA) are gaining interest and considerable attention of worldwide researchers of life sciences. Avian egg antibodies constitute a good source of beneficial antibodies as immunized hens could lay large number of eggs in a period of time containing a high concentration of antibodies in their yolk contents 8-11 . The immunologically active proteins and peptides of IgY and its immunomodulatory mechanisms have been recognized 12-14 The use of transgenic chickens producing antibodies in the egg ovalbumin has provided bioreactor hens as a good source of avian egg antibodies 15,16 The avian eggs act as efficient repositories for promising antigen-specific antibodies having numerous biomedical applications to be used in immunodiagnostics, proteomics and in immunotherapy for combating infectious diseases 17-20 Apart from useful treatment options in humans the EYA have proved their potent prophylactic and therapeutic applications in combating several infectious diseases including of bacterial and viral origin in animals and fish/aquatic animals 7,21-28 . Passive immunization using avian egg antibodies (IgY) has been found to be effective in providing protection against several pathogens affecting animals and humans viz., Helicobacter pylori in humans, bovine and human rotaviruses, bovine coronavirus, Listeria monocytogenes , Escherichia coli , Salmonella , Staphylococcus and Pseudomonas spp., poultry pathogens such as Salmonella , Campylobacter , infectious bursal disease (Gumboro) virus and newcastle disease virus; fish and aquatic pathogens like shrimp white spot syndrome virus (WSSV), Yersinia ruckeri , Edwardsiella tarda , Aeromonas salmonicida, Vibrio alginolyticus, Vibrio anguillarum, Shewanella putrefaciens and Pseudomonas fluorescens 17,27,29-33 . The IgY acts by enhancing the phagocytic ability macrophages and inhibition of growth and colonization of bacteria 19,31 Agglutination, adherence-blockade, opsonization, inhibition of enzymatic activity and toxin neutralization are other mechanism of action of IgY 27 . The IgY could also serve as a valuable alternative to antibiotics for treating antibiotic-resistant microbial pathogens. Avian egg yolk antibodies could also be useful in food preservation as natural antimicrobial agents. Since, IgY is suitably stable in saliva, thus can be used to treat certain localized infections related to oral mucosa 19 . Apart from above utilities, IgY can also be employed as growth promoting agent as observed in fish by using antibodies against several neuropeptides of gut such as cholecystokinin and neuropeptide Y 19 A recent systematic review and meta-analysis demonstrated that the beneficial effects of IgY for prophylaxis and therapeutic purposes. With regards to this, more explorative research studies are needed to be performed utilizing the gold standard animal experiments with an aim to bring into play IgY alone or in combination options with supplementary alternative measures to be adapted 32 Reports regarding beneficial applications of IgY in fish are very limited as compared to animals (Calves, lamb and goat, cats and dogs), poultry and humans. This study describes the potential immunotherapeutic applications of avian egg yolk antibodies (IgY) for the prevention and treatment of enteric diseases of fish and aquatic animal species along with key features and advantages as well as speculating the future prospects of IgY technology. The information compiled will be beneficial for fish professionals, researchers and pharmaceutical industry to design and develop novel alternative therapeutic and prophylactic module utilizing the tremendous abilities of IgY antibodies for safeguarding health of fish and aquatic animals as well in promoting the various avenues of this promising technology POTENT ADVANTAGES OF AVIAN EGG YOLK ANTIBODIES (IgY) After immunization, specific IgY antibodies are continuously synthesized, excreted into the blood of the hen and then transferred from blood/serum into the egg yolk. The major antibody produced by chickens is immunoglobulin IgY that provides necessary immunity to the progeny chicks in terms of passive humoral immunity required against various pathogens in early days of chicks until complete maturation of their immune system 18 Laying chickens are used as immunization host for a specific antigen of interest encoding the targeted protein for the generation of specific and biologically active egg yolk immunoglobulins (IgY) which are vertically transmitted from their serum into the egg yolk from where they can be extracted and purified and used as an alternative source of 761

Int. J. Pharmacol., 12 (8): 760-768, 2016 antibodies for the prevention and treatment of infectious enteric diseases. Laying hens are very efficient producers of specific antibodies. Nearly 280-300 eggs are being laid by a hen in a year with 100-150 mg IgY per egg yolk which could give 20-40 g IgY per year through eggs of a bird 29,34 . Thus an egg can be considered as a small "Factory" for antibody production. Further, use of chicken eggs as source of antibody, reduces the number of experimental animals such as mice, rabbit for research purpose, which is very much required today for the sake of animal welfare and solving the problem of animal ethics issues 34 . Oral administration of IgY have been useful in controlling infectious diseases of bacterial and viral origin 35,36 . Oral administration of IgY possesses many advantages over the use of mammalian IgG including cost-effectiveness, convenience and higher yield 27 . The IgY is non-toxic, without any residual and negative effect to the environment Usage of IgY technology has several advantage viz., non-invasive antibody harvesting procedures avoids concerns regarding the welfare of the immunized animals, as the IgY antibodies can be separated without sacrificing chickens, convenience of simple egg collection, rapid and simple IgY isolation from egg yolks, a good alternative to conventional polyclonal antibody production in mammals 37 . Chickens possess numerous advantages over mammals to be used as hosts for immunization, especially their phylogenetic distance, modes of immune diversification and the means by which IgY immunoglobulin is deposited in the egg yolk and showing remarkable high affinity, avidity and highly neutralizing abilities for an infectious pathogen 38 . Also, chicken requires less quantity of antigen to stimulate and produce specific antibodies (approximately 2-10%) than mammals (only about 5%) 29 . The stability of IgY in the oro-gastrointestinal tract and its safety issues are well proven, while the stability of IgY can further be enhanced by encapsulating with alginate microcapsules which protects it from the action of low pH gastric juices 39 . Mammalian sera contains many classes of antibodies after immune stimulation with single antigen whereas egg yolk consist of only single class of antibody i.e., IgY, thus facilitating ease of purification 29 . One-step purification of IgY antibodies in large amounts from egg yolk provides a practical continuous supply, epitope spectrum of IgY potentially facilitates novel specificities, lack of serological cross-reactivity with mammalian epitopes, Fc receptors and complement steer clear of interference during assays and potentiates the outcome of immunological methods adapted as well avoids mediation of inflammatory responses during their usages 17,20,34 . Thus IgY can be used as long term therapeutic agent without any negative effects on animal health 19 . Because IgY are resistant to the gastric barrier, these are of particular interest for passive immunotherapy of gastrointestinal tract infections. Added to these, eggs being normal dietary element with no religious taboo issues so pose practically no risk of toxic side effects of IgY antibodies However, it is important to analyze the allergic reactions as observed by consumption of egg protein in some individuals 34 . But it has been suggested that the IgY is not associated with any risk of causing allergic reactions 31 As chickens are less costly, egg yolk antibodies can be produced in a more cost effective and easy manner compared with production of antibodies from mammals and also have preferred advantages in their various applications including usage in immunodiagnostics and immunotherapeutics 18,29 Unlike mammalian IgG, IgY antibody does not react with rheumatoid factor hence, no false positive result in rheumatoid immunoassay 37 . The IgY preparations in egg yolk powder, purified powder and liquor may offer a practicable and noteworthy applications of avian egg antibodies. It has also been demonstrated that IgY antibodies can be used to prevent rejection in case of xenotransplantation thus, can be looked upon as potential solution of overcoming transplantation failure 37 . Also, IgY can be used to overcome the problem of zoonotic infections such as cryptosporidium infection and bioterrorism 19,34 . Apart from containing IgY, egg yolk contains other anti-infectious agents which gives additional benefit to the patients 18 . Salient advantages of avian egg yolk antibodies (IgY) over the conventional antibodies are depicted in Fig. 1. Figure 1 depicts various advantages of IgY technology over the conventional antibodies. Advantages include: Non invasive antibody harvesting, egg collection easy, cost effective, IgY is non toxic, non allergic etc The "DNA-designed" avian IgY antibodies produced via immunization with a gene vector expressing a corresponding antibody in situ avian host cells allows direct generation of IgY antibodies from a plasmid DNA that could avoid the cumbersome procedures for obtaining purified antigens in a conventional antibody production system 40 . Use of various adjuvants such as CpG ODN has been found to enhance antibody production with DNA vaccines 41 . The IgY obtained by DNA immunization has a closely related epitope pattern to that observed in virtual viral infection. A quick and inexpensive production of antibodies will provide pertinent tools to link the fields of genomics and proteomics. However, polyclonal 762

Int. J. Pharmacol., 12 (8): 760-768, 2016 Fig. 1: Advantages of avian egg yolk antibodies (IgY) nature of IgY antibodies could limit their use. In such circumstances, recombinant IgY can be created from mammalian monoclonal antibodies that would facilitate further utilization of many benefits of the IgY technology 20 THERAPEUTIC APPLICATIONS AGAINST INFECTIOUS DISEASES OF FISH/AQUATIC ANIMALS Specific IgY has been found to have effective therapeutic values to control various bacterial and virus pathogens in fish and aquatic animals 21,27 . The EYA has been found effective in diseases like White Spot Disease (WSD) in shrimps and crayfishes, Vibrio anguillarum and Yersinia ruckeri in rainbow trout, Aeromonas hydrophila in polyploid gibel carps ( Carassius auratus gibelio ), Edwardsiellosis in Japanese eel ( Anguilla japonica ) 23,41-47 Chicken IgY, against a truncated fusion protein of VP 28 and VP 19, have been found to neutralize WSSV which is an economically important pathogen causing high mortality and losses to cultured shrimp industry worldwide 44 . The IgY antibodies recovered from the egg yolk of chickens immunized with a DNA vaccine constituted with structural proteins genes of WSSV or with inactivated WSSV have been shown to demonstrate utility in passive immunization of shrimp by possessing a high affinity and neutralization activity for WSSV, good survival rate of experimentally challenged shrimps, particularly using the traditional inactivated vaccine 36 The immunization with specific IgY antibodies was found protective against this viral infection when administered through intramuscular injection, oral and immersion application in crayfish ( Procambius clarkiaii ) challenged with WSSV 36 . Thus prospective immunotherapeutic role of specific IgY in preventing this important infection in shrimp has been suggested Passive immunization with IgY has also been reported to be effective against Yersinia ruckeri, the causative agent of enteric redmouth disease (systemic bacterial septicaemia) affecting rainbow trout ( Oncorhynchus mykiss ); immunized fishes revealed lower mortality rate and fewer infections 43 Efficacy of EYA have been studied against Edwardsiella tarda infection, an important fish pathogen which spreads through the intestinal mucosa and IgY were found protective in preventing this infectious disease of fishes 21,42 . In a limited trial, specific IgY antibodies when simultaneously administered orally to Japanese eels with the E. tarda resulted in a good survival rate and with no disease symptoms 763 Non-invasive harvesting of antibody, no need to sacrifice the body Immuniztaion Alginate micro capsulated lgY Stability increased Simple isolation and purification process Acid in stomach Po ult ry p hy lo gen eti ca ll y di st an t Difference in immune system Collection of egg-simple Poultry requires lesser antigen for lgY production Production of lgY is cost effective Non toxic Non allergic No serological cross reactivity lgY Effective alternative to antibiotics since there is no development of resistance

Int. J. Pharmacol., 12 (8): 760-768, 2016 seen in IgY administered eels, which indicates an effective role of anti- E. tarda IgY in preventing edwardsiellosis 42 Li et al 45 showed that specific IgY immunoglobulin obtained from egg yolk of immunized white leghorn hens immunized against formalin inactivated Aeromonas hydrophila could provide protection rate of 60-70% in polyploid gibel carps. The ELISA confirmed that hyperimmune serum shows maximum IgY level 56 th day post-immunization and peak level was maintained till day 133 th. Similarly, in another study outcomes advocated that passive immunization of ayu, Plecoglossus altivelis by oral administration with pathogen-specific chicken IgY is a valuable means for controlling Vibrio anguillarum infection in ayu. Treatment with specific IgY isolated from egg yolks of hens immunized with formalin-inactivated V. anguillarum significantly enhanced the phagocytic activity of macrophages for V. anguillarum in the presence of specific IgY and decreased levels of tumor necrosis factor- α (PaTNF- α ), interleukin-1 β (PaIL-1 β ), transforming growth factor- β (PaTGF- β ) and leukocyte cell-derived chemotaxin-2 (PaLECT 2) and proved protective effect of IgY against V. anguillarum infection in the ayu 35 The IgY could be a useful strategy for the treatment of piscirickettsiosis against intracellular bacterial pathogen Piscirickettsia salmonis of fish when fishes were treated orally Specific IgY was produced by immunizing hens with P. salmonis proteins and purified from egg yolks by ammonium sulphate precipitation method. Specific IgY effectively inhibited the growth of P. salmonis by agglutination where IgY interacted with surface components of the pathogen. In vitro and in vivo studies showed that anti- P. salmonis IgY antibody reacted strongly and particularly against P. salmonis proteins with a positive protective effect 48 For passive immunization of gastric rainbow trout ( Oncorhynchus mykiss ) and a gastric common carp ( Cyprinus carpio ) when IgY antibodies were administered orally their protective potential was found higher as they can cross the gastric barriers to maintain the plasma level in the body 49,50 Similarly, passive immunization of ornamental koi carp induced by immersing fish into aquarium water containing specific anti- Aeromonas salmonicida IgY provided significant protection against A. salmonicida infection with reduced clinical signs of skin ulceration and disfiguring ornamental fish 51 . Hence, use of chicken IgY in the ornamental fish industry is a novel means of prospective prophylaxis against pathogens attacking the skin and gills of fishes from cohabitation infection by immersing fishes into specific IgY containing rearing water. The V. alginolyticus can cause huge economic loss by causing death of small abalone. The IgY against V. alginolyticus was encapsulated with alginate and it was incorporated into basal diet of small abalone at 5, 10% and a control group without IgY treatment was also included in the study. Alginate encapsulation increased the stability of IgY in the gastrointestinal tract of the shellfish IgY treated group had a survivability ranging from 65-70% post challenge after 14 days with 1×10 CFU 39 . Other researcher through separated studies confirmed that specific immunoglobulins from hen egg yolk are promising novel alternative approach for disease control in fishes caused by variety of microorganism 39,49,51 Vibrio splendidus is an importnat pathogen causing skin ulceration syndrome in sea cucumber ( Apostichopus japonicus ). In a recent study, IgY against V . splendidus was produced by two step salt precipitation and ultrafiltration in white leghorn chicken. Purity of IgY was 83% and its was injected intraperitoneally in sea cucumber at a concentration of 10 mg mL G 1 or sea cucumberʼs were immersed in IgY of 1 mg mL G 1 . Survival of the tested sea cucumbers was analyzed and it was found that intraperitoneal injection resulted in 80% protection while immersion resulted in 75% protection. Similarly the burden of bacteria in IgY treated sea cucumber was also less in the respiratory tract and intestine when compared with untreated control. Thus this study revealed the potential of IgY against V. splendidus infection 52 Specific IgY displayed significant antimicrobial activity to prolong the shelf life of refrigerated fish and prevent spoilage of fishery food from specific spoilage organisms (SSO) such as Shewanella putrefaciens and Pseudomonas fluorescens under aerobic chilling storage conditions and now antigen-binding fragment plus the hinge region (IgY-Fab') is also considered a promising tool for improving the efficiency of natural antimicrobial agents 53 . The IgY-Fab' demonstrated higher and more durable antimicrobial potential by effectively inhibiting the bacterial growth and prolonging the shelf life of marine products more efficiently as a novel strategy for fish preservation. Significant broad spectrum antimicrobial activity of the anti-SSO IgY extended the shelf life of refrigerated fish products from 9-15 days in the presence of the specific IgY and demonstrated its bio-preservative potential for seafood and marine products 54 . Potential therapeutic application of IgY in countering infectious diseases of fish and aquaculture animals is presented in Fig. 2. The WSSV recombinant protein or DNA vaccine of WSSV 764

Int. J. Pharmacol., 12 (8): 760-768, 2016 Fig. 2: Use of IgY in aquaculture is used to raise anti WSSV IgY which when administered to shrimp and crayfish, protects from WSD. Yersinia ruckeri causes red mouth disease in rainbow trout. IgY against Y. rukeri reduces infection and mortality caused by Y. rukeri E. tarda infects intestinal mucosa of Japanese eel Administration of anti E. tarda IgY neutralizes the bacteria and eliminates the symptoms. Similarly, IgY antibodies has been used with good results against various pathogens like Piscirickettsia salmonis, Aeromonas hydrophila, Aeromonas salmonicida, Vibrio alginolyticus , Vibrio anguillarum , Shewanella putrefaciens and Pseudomonas fluorescens (Fig. 2) POTENTIAL LIMITATIONS OF IgY Numerous advantages support the use of IgY in human and veterinary field, however there are some shortfalls that needs to be strengthened so that this technology can be used to great success. Major drawback is the proteolytic disintegration of IgY in gastric conditions when administrated through oral route. Studies conducted in eels showed that IgY could resist the digestive environment but when the pH is less than 3, activity of IgY is completely lost 21,55,56 . Small intestine is the area of absorption of IgY but they do not resist the acidic environment of the stomach. Hence methods that can protect the IgY from acidic pH and carry towards the site of absorption is essential. One such method is encapsulation using alginate or any other method can prevent the IgY from acidic pH 39 . This method seems to be a better option for preventing the proteolysis but they are cost effective hence it is difficult to employ at commercial level. Studies also report that IgY can be used as prophylactic agent against specific bacterial infection rather than as a therapeutic agent 42 CONCLUSION AND FUTURE PROSPECTS The tremendous potential of avian eggs as valuable repository of promising immunotherapeutic antibodies (IgY) needs to be explored to their full potential against harmful effects of various infectious pathogens and safeguard health of viable fish/aquatic animals. Increasing problems of emerging bacterial resistance issue and the presence of drug residues in fish products poses food safety and public health concerns. In this scenario, EYA could provide a viable option due its potent therapeutic avenues. Application of EYA 765 White spot syndrome virus VP 19 VP 28 Recombinant protein Truncated VP 28/ VP 19+fusion protein DNA vaccine with structural protein Immunization of Y. rukeri antigens Immunizing chicken with truncated proteins lgY administration to rainbow trouts Shrimp Rainbow trout in pond Red mouth disease E. tarda affects the intestinal mucosa Infection and mortality reduced Administration of lgY through any route Protects shrimp against WSSV lgY neutralized E. tarda infection-no clinical symptomps lgY acts with surface components-inhibiting P. salmonis growth lgY administration Intracellular pathogen Intestinal mucosa of Japanese eels Rain bow tr ou t lgY immu ni zat ion to e el Edwardsiella tarda Piscirickettsia salmonis Yersinia ruckeri lgY antibodies has been effectively used against other fish pathogens like Aeromonas hydrophila , Aeromonas salmonicida , Vibrio alginolyticus , Vibrio anguillarum , Shewanella putrefaciens and Pseudomonas fluorescens

Int. J. Pharmacol., 12 (8): 760-768, 2016 immunization is a labor intensive procedure and might have limited applications in commercial aquaculture conditions and fishes/aquatic animal species raised in the ocean. The oral administration of specific IgY to counter fish pathogens could provide a valuable alternative method to antibiotics/chemotherapy for prevention of diseases in fish farms. Thus, oral IgY antibodies could offer very promising possibilities for useful passive immunization strategies in the years to come and added to this the usage of IgY as feed additive and immersion solutions may give rise to useful practicable methods for its potent applications to be implemented effectively in prevention and control of infectious diseases of fish. Various laboratory studies and clinical trials of IgY supplemented foods for disease prevention and control purposes have been reported. It is a very powerful alternative in the current scenario of flaring up antibiotic resistant microbes. These have gained much interest of worldwide researchers for exploration as an inexpensive non-antibiotic alternative approach for the treatment and prevention of a wide variety of infectious diseases The IgY therapeutic applications are highly encouraging and further work would pave into the market the entry of novel commercial nutraceuticals or health supplements based on the utility of mono-specific or mixed IgY formulations. Consumer preferences for natural resources to lessen health issues, medicinal costs and the recent move ahead in drug delivery systems and combinational therapeutic regimens it is likely the usage and applications of IgY may swing from functional food category towards development of novel pharmaceuticals in the near future. However, some controversy with regards to the stability of IgY in the GI tract by discovering an effectual way to protect such antibodies from degradation during usage would pave considerable advances in practical directions for optimum utilization of IgY technology and its numerous nutraceutical and therapeutic applications. Though applications of IgY antibodies in fish and aquatic animals have shown a new path for managing the emerging problems posed through infectious pathogens, strengthening of research activities are suggested to see the virtual benefits of EYA in fish and aquatic industry. Additional and future studies can be directed to mode of action of EYA in fish, residue of the antibodies in the body, determination of appropriate dose and suitable formulations in the fish diet and probably side effects of EYA for aquatic animals. There is also need to compare use of IgY antibodies along with other immunostimulant drugs for enhancing effectiveness, feasibility and productivity aspects. Furthermore, commercialization and market attitude should be considered seriously in propagation and consumption of mentioned products in the future ACKNOWLEDGMENTS Authors of the manuscript thank and acknowledge their respective Institutes REFERENCES 1 Dhama, K., M.S. Basaraddi, R. Tiwari and L.R. Ananthakrshna, 2011. Egg Yolk Antibodies (EYA): Applications in poultry Poult. Technol., 6: 20-24 2 Dhama, K., S. Chakraborty, M.Y. Wani, R. Tiwari and R. Barathidasan, 2013. Cytokine therapy for combating animal and human diseases-A review. Res. Opin. Anim. Vet Sci., 3: 195-208 3 Dhama, K., S. Chakraborty, Mahima, M.Y. Wani and A.K. Verma et al ., 2013. Novel and emerging therapies safeguarding health of humans and their companion animals: A review. Pak. J. Biol. Sci., 16: 101-111 4 Mahima, A. Rahal, R. Deb, S.K. Latheef and H.A. Samad et al ., 2012. Immunomodulatory and therapeutic potentials of herbal, traditional/indigenous and ethnoveterinary medicines. Pak. J. Biol. Sci., 15: 754-774 5 Malik, Y.S., K. Sharma, L.M. Jeena, N. Kumar, S. Sircar, K.K. Rajak and K. Dhama, 2013. Toll-like receptors: The innate immune receptors with ingenious anti-viral paradigm. South Asian J. Exp. Biol., 3: 207-213 6 Tiwari, R., S. Chakraborty, K. Dhama, S. Rajagunalan and S.V. Singh, 2013. Antibiotic resistance-an emerging health problem: Causes, worries, challenges and solutions: A review Int. J. Curr. Res., 5: 1880-1892 7 Tiwari, R., S. Chakraborty, K. Dhama, M.Y. Wani, A. Kumar and S. Kapoor, 2014. Wonder world of phages: Potential biocontrol agents safeguarding biosphere and health of animals and humans-current scenario and perspectives. Pak J. Biol. Sci., 17: 316-328 8 Larsson, A., R.M. Balow, T.L. Lindahl and P.O. Forsberg, 1993 Chicken antibodies: Taking advantage of evolution-a review Poult. Sci., 72: 1807-1812 9 Carlander, D., M. Wilhelmson and A. Larsson, 2003 Immunoglobulin Y levels in egg yolk from three chicken genotypes. Food Agric. Immunol., 15: 35-40 10. Michael, A., S. Meenatchisundaram, G. Parameswari, T. Subbraj, R. Selvakumaran and S. Ramalingam, 2010 Chicken egg yolk antibodies (IgY) as an alternative to mammalian antibodies. Indian J. Sci. Technol., 3: 468-474 11. Rossi, M., Y. Nys, M. Anton, M. Bain and B. de Ketelaere et al ., 2013. Developments in understanding and assessment of egg and egg product quality over the last century. Worldʼs Poult Sci. J., 69: 414-429 766

Int. J. Pharmacol., 12 (8): 760-768, 2016 12. Polanowski, A., A. Zablocka, A. Sosnowska, M. Janusz and T. Trziszka, 2012. Immunomodulatory activity accompanying chicken egg yolk immunoglobulin Y. Poult. Sci., 91: 3091-3096 13. Polanowski, A., A. Sosnowska, A. Zablocka, M. Janusz and T. Trziszka, 2013. Immunologically active peptides that accompany hen egg yolk immunoglobulin Y: Separation and identification. Biol. Chem., 394: 879-887 14. Zablocka, A., A. Sosnowska, A. Urbaniak, M. Janusz and A. Polanowski, 2014. Peptides accompanying chicken egg yolk IgY-alternative methods of isolation and immunoregulatory activity. Food Funct., 5: 724-733 15. Nishijima, K.C. and S. Iijima, 2013. Transgenic chickens. Dev Growth Differ., 55: 207-216 16. Miao, X., 2013. Recent advances in the development of new transgenic animal technology. Cell. Mol. Life Sci., 70: 815-828 17. Larsson, A. and D. Carlander, 2003. Oral immunotherapy with yolk antibodies to prevent infections in humans and animals. Upsala J. Med. Sci., 108: 129-140 18. Da Silva, W.D. and D.V. Tambourgi, 2010. IgY: A promising antibody for use in immunodiagnostic and in immunotherapy. Vet. Immunol. Immunopathol., 135: 173-180 19. Kovacs-Nolan, J. and Y. Mine, 2012. Egg yolk antibodies for passive immunity. Annu. Rev. Food Sci. Technol., 3: 163-182 20. Spillner, E., I. Braren, K. Greunke, H. Seismann, S. Blank and D. du Plessis, 2012. Avian IgY antibodies and their recombinant equivalents in research, diagnostics and therapy. Biologicals, 40: 313-322 21. Hatta, H., K. Mabe, M. Kim, T. Yamamoto, M. Gutierrez and T. Miyazaki, 1994. Prevention of Fish Disease Using Egg Yolk Antibody. In: Egg Uses and Processing Technologies: New Developments, Sim, J.S. and S. Nakai (Eds.). CAB International, Wallingford, ISBN: 978-0851988665, pp: 241-249 22. Kweon, C.H., B.J. Kwon, S.R. Woo, J.M. Kim and G.H. Woo et al ., 2000. Immunoprophylactic effect of chicken egg yolk immunoglobulin (Ig Y) against Porcine Epidemic Diarrhea Virus (PEDV) in piglets. J. Vet. Med. Sci., 62: 961-964 23. Arasteh, N., A.H. Aminirissehei, A.N. Yousif, L.J. Albright and T.D. Durance, 2004. Passive immunization of rainbow trout ( Oncorhynchus mykiss ) with chicken egg yolk immunoglobulins (IgY). Aquaculture, 231: 23-36 24. Kovacs-Nolan, J. and Y. Mine, 2004. Avian egg antibodies: Basic and potential applications. Avian Poult. Biol. Rev., 15: 25-46 25. Schade, R., E.G. Calzado, R. Sarmiento, P.A. Chacana, J. Porankiewicz-Asplund and H.R. Terzolo, 2005. Chicken egg yolk antibodies (IgY-technology): A review of progress in production and use in research and human and veterinary medicine. Altern. Lab. Anim., 33: 129-154 26. Yegani, M. and D.R. Korver, 2010. Application of egg yolk antibodies as replacement for antibiotics in poultry. Worldʼs Poult. Sci. J., 66: 27-38 27. Xu, Y., X. Li, L. Jin, Y. Zhen and Y. Lu et al ., 2011. Application of chicken egg yolk immunoglobulins in the control of terrestrial and aquatic animal diseases: A review. Biotechnol. Adv., 29: 860-868 28. Trziszka, T., H. Rozanski and A. Polanowski, 2013. Eggs as a very promising source of biomedical and nutraceutical preparations: A review. J. Life Sci., 7: 862-877 29. Mine, Y. and J. Kovacs-Nolan, 2002. Chicken egg yolk antibodies as therapeutics in enteric infectious disease: A review. J. Med. Food, 5: 159-169 30. Sui, J., L. Cao and H. Lin, 2011. Antibacterial activity of egg yolk antibody (IgY) against Listeria monocytogenes and preliminary evaluation of its potential for food preservation. J. Sci. Food Agric., 91: 1946-1950 31. Rahman, S., S. van Nguyen, F.C. Icatlo Jr., K. Umeda and Y. Kodama, 2013. Oral passive IgY-based immunotherapeutics: A novel solution for prevention and treatment of alimentary tract diseases. Hum. Vaccines Immunotherapeut., 9: 1039-1048 32. Diraviyam, T., B. Zhao, Y. Wang, R. Schade, A. Michael and X. Zhang, 2014. Effect of chicken egg yolk antibodies (IgY) against diarrhea in domesticated animals: A systematic review and meta-analysis. PloS One, Vol. 9. 10.1371/journal.pone.0097716. 33. Wang, B., J. Yang, S. Cao, H. Wang and X. Pan et al ., 2014 Preparation of specific anti- Helicobacter pylori yolk antibodies and their antibacterial effects. Int. J. Clin. Exp. Pathol., 7: 6430-6437 34. Carlander, D., H. Kollberg, P.E. Wejaker and A. Larsson, 2000 Peroral immunotheraphy with yolk antibodies for the prevention and treatment of enteric infections. Immunol. Res., 21: 1-6 35. Li, C.H., X.J. Lu, D.F. Li and J. Chen, 2014. Passive protective effect of chicken egg yolk immunoglobulins against experimental Vibrio anguillarum infection in ayu ( Plecoglossus altivelis ). Fish Shellfish Immunol., 37: 108-114 36. Lu, Y., J. Liu, L. Jin, X. Li and Y. Zhen et al ., 2009. Passive immunization of crayfish ( Procambius clarkiaii ) with chicken egg yolk immunoglobulin (IgY) against White Spot Syndrome Virus (WSSV). Applied Biochem. Biotechnol., 159: 750-758 37. Tini, M., U.R. Jewell, G. Camenisch, D. Chilov and M. Gassmann, 2002. Generation and application of chicken egg-yolk antibodies. Comp. Biochem. Physiol. A: Mol. Integr. Physiol., 131: 569-574 38. Narat, M., 2003. Production of antibodies in chickens. Food Technol. Biotechnol., 41: 259-267 39. Wu, C.J., H. Wang, Y.L. Chan and T.L. Li, 2011. Passive immune-protection of small abalone against Vibrio alginolyticus infection by anti-Vibrio IgY-encapsulated feed Fish Shellfish Immunol., 30: 1042-1048 40. Cova, L., 2005. DNA-designed avian IgY antibodies: Novel tools for research, diagnostics and therapy. J. Clin. Virol., 34: S 70-S 74 767

Int. J. Pharmacol., 12 (8): 760-768, 2016 41. Lu, Y, J. Liu, L. Jin, X. Li and Y. Zhen et al ., 2008. Passive protection of shrimp against White Spot Syndrome Virus (WSSV) using specific antibody from egg yolk of chickens immunized with inactivated virus or a WSSV-DNA vaccine. Fish Shellfish Immunol., 25: 604-610 42. Gutierrez, M.A., T. Miyazaki, H. Hatta and M. Kim, 1993 Protective properties of egg yolk IgY containing anti- Edwardsiella tarda antibody against paracolo disease in the Japanese eel, Anguilla japonica Temminck and Schlegel J. Fish Dis., 16: 113-122 43. Lee, S.B., Y. Mine and R.M.W. Stevenson, 2000. Effects of hen egg yolk immunoglobulin in passive protection of rainbow trout against Yersinia ruckeri . J. Agric. Food Chem., 48: 110-115 44. Kim, D.K., I.K. Jang, H.C. Seo, S.O. Shin, S.Y. Yang and J.W. Kim, 2004. Shrimp protected from WSSV disease by treatment with egg yolk antibodies (IgY) against a truncated fusion protein derived from WSSV. Aquaculture, 237: 21-30 45. Li, X.L., J.B. Shuai and W.H. Fang, 2006. Protection of Carassius auratus Gibelio against infection by Aeromonas hydrophila using specific immunoglobulins from hen egg yolk. J. Zhejiang Univ. Sci. B, 7: 922-928 46. Fu, L.L., Y. Wang, J.R. Li and W.F. Li, 2010. Protection of Fenneropenaeus chinensis (Osbeck, 1765) against the white spot syndrome virus using specific chicken egg yolk immunoglobulins by oral delivery. Aquacult. Res., 41: 1806-1816 47. Kumaran, T., M. Michaelbabu, T. Selvaraj, S. Albindhas and T. Citarasu, 2010. Production of anti WSSV IgY edible antibody using herbal immunoadjuvant Asparagus racemosus and its immunological influence against WSSV infection in Penaeus monodon . J. Aquacult. Feed Sci. Nutr., 2: 1-5 48. Oliver, C., K. Valenzuela, H. Silva, R.E. Haro and M. Cortes et al ., 2015. Effectiveness of egg yolk immunoglobulin against the intracellular salmonid pathogen Piscirickettsia salmonis J. Applied Microbiol., 119: 365-376 49. Winkelbach, A., D. Gunzel, C. Schulz and S. Wuertz, 2015 Differences in IgY gut absorption in gastric rainbow trout ( Oncorhynchus mykiss ) and agastric common carp ( Cyprinus carpio ) assessed in vivo and in vitro . Comp Biochem. Physiol. Part C: Toxicol. Pharmacol., 167: 58-64 50. Winkelbach, A., S. Wuertz, R. Schade, P.T. Witkowski and A. Steibli et al ., 2016. Effects of oral passive immunization against somatostatin-14 on growth performance, body composition and IgY delivery in rainbow trout ( Oncorhynchus mykiss ) and common carp ( Cyprinus carpio ) Aquacult. Nutr., (In Press). 10.1111/anu.12404 51. Gan, H., H. He, A. Sato, H. Hatta, M. Nakao and T. Somamoto, 2015. Ulcer disease prophylaxis in koi carp by bath immersion with chicken egg yolk containing anti- Aeromonas salmonicida IgY. Res. Vet. Sci., 99: 82-86 52. Li, X., K. Jing, X. Wang, Y. Li and M. Zhang et al ., 2016 Protective effects of chicken egg yolk antibody (IgY) against experimental Vibrio splendidus infection in the sea cucumber ( Apostichopus japonicus ). Fish Shellfish Immunol., 48: 105-111 53. Xu, Y., H. Lin, J. Sui and L. Cao, 2012. Effects of specific egg yolk antibody (IgY) on the quality and shelf life of refrigerated Paralichthys olivaceus . J. Sci. Food Agric., 92: 1267-1272 54. Zhang, Q., H. Lin, J. Sui, J. Wang and L. Cao, 2015. Effects of Fab' fragments of specific egg yolk antibody (IgY-Fab') against Shewanella putrefaciens on the preservation of refrigerated turbot. J. Sci. Food Agric., 95: 136-140 55. Shimizu, M., R.C. Fitzsimmons and S. Nakai, 1988. Anti- E. coli immunoglobulin Y isolated from egg yolk of immunized chickens as a potential food ingredient. J. Food Sci., 53: 1360-1366 56. Dhama, K., Y.S. Malik, K. Karthik, R. Tiwari and S. Chakraborty, 2015. Emerging therapies and their benefits to animals and humans. Indian Farming, 64: 40-42 768

Other Health Sciences Concepts:

[back to top]

Discover the significance of concepts within the article: ‘Avian Egg Yolk Antibodies (IgY) and their Potential Therapeutic Applications...’. Further sources in the context of Health Sciences might help you critically compare this page with similair documents:

Major drawback, Gastric juice, Therapeutic application, Infectious disease, Gastrointestinal Tract, Animal welfare, Pharmaceutical industry, Rheumatoid factor, Drug delivery system, Antimicrobial activity, Food safety, Antimicrobial agent, Oral mucosa, Escherichia coli, ALLERGIC REACTION, Helicobacter pylori, Intestinal mucosa, Passive immunization, Immunized chickens, Spoilage organisms, Experimental animal, Natural antimicrobial agent, Vibrio alginolyticus, Chicken egg yolk antibodies, Gastrointestinal tract infection, Tumor necrosis factor, Xenotransplantation, Aeromonas salmonicida, Immersion solutions, Zoonotic infection, DNA vaccine, Emerging therapies, Egg yolk antibodies, Feed additive, Macrophage, Ornamental fish industry, Oral passive immunization, Health supplement, Enteric disease, Immunotherapeutic, Serological cross-reactivity, Antigen-specific antibodies, Growth promoting agent, Phylogenetic distance, Dietary element, Prophylactic applications.