Oral administration of specific antibodies is an attractive approach to establish protective immunity against gastrointestinal pathogens in humans and animals. The increasing number of antibiotic-resistant bacteria emphasize the need to find alternatives to antibiotics. Immunotherapy can also be used against pathogens that are difficult to treat with traditional antibiotics. Laying hens are very good producers of specific antibodies. After immunization, the specific antibodies are transported to the egg yolk from which the antibodies then can be purified. A laying hen produces more than 20 g of yolk antibodies (IgY) per year. These antibodies also have biochemical properties that make them attractive for peroral immunotherapy: They neither activate mammalian complement nor interact with mammalian Fc receptors that could mediate inflammatory response in the gastrointestinal tract. Eggs are also normal dietary components and thus there is practically no risk of toxic side effects of IgY. Yolk antibodies have been shown in several studies to prevent bacterial and viral infections.

Respiratory infection is the major cause of morbidity and mortality in cystic fibrosis (CF) patients. Chronic Pseudomonas aeruginosa (PA) infections ultimately occur in virtually all patients. It is impossible to eradicate PA when a patient has been chronically colonized. Immunotherapy with specific egg-yolk antibodies (IgY) may be an alternative to antibiotics for the prevention of PA infections. We wanted to determine if treatment with specific IgY can prolong the period between the first and the second PA colonization? And long-term, can the treatment diminish the number of positive PA cultures and postpone the onset of chronic colonization? CF patients gargled daily with an IgY-antibody preparation, purified from eggs of hens immunized with PA bacteria. They were compared to a group of patients who did not gargle with the preparation. Both groups had their first colonization with PA eradicated by antibiotics. The basic treatment was essentially the same in both groups. In the initial study, the period between the first and second colonization with PA was significantly prolonged for the treated vs. the control group (Kaplan-Meier P = 0.015, Breslow test). In the prolonged study, the treated group had only 2.5 sputum cultures positive for PA per 100 months of observation, and none of these patients became chronically colonized with PA. No adverse events were reported. In the control group, 13.7 cultures per 100 months of observation were positive for PA, and 5 (24%) patients became chronically colonized with PA. This feasibility study shows that antipseudomonal IgY has the potential to effectively prevent PA colonization without any severe adverse effects. A phase III study should be initiated.

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The chicken immune system has been studied for many years and these studies have contributed substantially to our understanding of the fimdamental concepts of immunology and the development of different immunoglobulin classes It is thus surprising that only a small fraction of the antibodies presently used in laboratories are of avian origin A laying hen produces more yolk antibodies than a rabbit can produce during the same time period, and the animal care costs are lower for the chicken compared to the rabbit Chicken antibodies offer many advantages to the traditional mammalian antibodies when used for the detection of mammalian antigen Due to the evolutionary difference chicken IgY will react with more epitopes on a mammalian antigen, which will give an amplification of the signal Chicken antibodies can also be used to avoid interference in immunological assays caused by the human complement system, rheumatoid factors, human anti-mouse IgG antibodies (HAMA) or human and bacterial Fc-receptors The antibodies can be purified in large amounts from egg yolk, making laying hens highly efficient producers of polyclonal antibodies IgY is an ancestor to mammalian IgG and IgE and also to IgA. ANTIBODY DIVERSITYThe antibody diversity in chicken differ from mammals and is mainly due to somatic hyperconversion. Rearrangement apparently contributes little to the diversity as both the heavy and the light chain loci consist of only one functional V gene (38,44). There seems to be a deficiency in the mechanism for selecting higher-affinity somatic mutants.Chicken antibody has the valency of 2.0 and sometimes higher which might be due to large antigen-binding sites (43). Most chicken IgY bind antigen strongly but display precipitation properties only at raised salt concentrations (16). The poor precipitation properties might be due to steric hindrance of the Fab arms to crosslink epitopes of two large antigens. The conditions permitting precipitation (salt -1.5 M) might loosen the restricted movement of the Fab arms and give functional independence to the binding sites. I80 ADVANTAGES OF CHICKEN ANTIBODIESAs the difference between the antigen and the immunized animal increases, the immune response usually increases. There is a vast phylogenetic difference between avian and mammalian species compared to the difference between two mammalian species. This evolutionary spread means that there is no immunological cross-reactivity between chicken IgY and mammalian IgG (18). Thus, chicken should be a better choice than e.g. rabbits for the production of antibodies against mammalian proteins. Due to evolutionary differences chicken antibodies will bind to more epitopes on a mammalian protein than the corresponding mammalian antibody. It has been shown that 3-5 times more chicken antibody than swine antibody will bind to rabbit IgG (1 7), which will amplify the signal (35). Chicken antibodies also recognize other epitopes than mammalian antibodies (41).This gives access to a different antibody repertoire than the traditional m...

Orange peel is a rich source of flavonoids with polymethoxyflavones as major constituents, compounds associated with potential antioxidant, anti-inflammatory, and antitumor activities. We studied the effect of an orange peel extract (OPE) on intestinal tumor growth in Apc(Min/+) mice, a mouse model for human familial adenomatous polyposis (FAP). The OPE contained 30% polymethoxyflavones, a mixture that included tangeretin (19.0%), heptamethoxyflavone (15.24%), tetramethoxyflavone (13.6%), nobiletin (12.49%), hexamethoxyflavone (11.06%), and sinensitin (9.16%). Apc(Min/+) mice were fed one of four diets: (1) AIN-76A control diet; (2) a new Western-style diet (NWD), i.e., AIN-76A diet modified with decreased calcium, vitamin D, and methyl-donor nutrients and increased lipid content); (3) NWD with 0.25% OPE; and (4) NWD with 0.5% OPE, with all additives premixed in the diet. After 9 weeks of feeding NWD to the Apc(Min/+) mice, tumors increased mainly in the colon, with tumor multiplicity increasing 5.3-fold and tumor volume increasing 6.7-fold. After feeding 0.5% OPE in NWD, the development of tumors markedly decreased, with multiplicity decreasing 49% in the small intestine and 38% in the colon. NWD also led to increased apoptosis in intestinal tumors, and 0.5% OPE in NWD further increased apoptosis in tumors of the small and large intestine. Findings indicated that OPE inhibited tumorigenesis in this preclinical mouse model of FAP, and increased apoptosis may have contributed to this effect.