Oral passive IgY-based immunotherapeutics: a novel solution for prevention and treatment of alimentary tract diseases

Abstract

This commentary summarizes the laboratory investigations and clinical trials published recently involving per-oral application of IgY supplemented food for specific orogastrointestinal disease prevention and control purposes. The prolonged use and misuse of conventional antibacterial drugs has spawned antibiotic resistant microbes prompting scientists to search for other germ-killing options. In particular, the use of IgY as a novel mode of immunotherapy using oral chicken immunoglobulin (IgY) to confer passive immunity has gained much interest as an inexpensive non-antibiotic alternative for the prophylaxis and treatment of a wide variety of infectious diseases. The stability of IgY in the orogastrointestinal tract and its safety profile has been well-documented. IgY has been used in the treatment or prevention of dental caries, periodontitis and gingivitis, gastritis and gastric ulcer, oral thrush and infant rotavirus diarrhea. The recent clinical trials on IgY with encouraging results has catapulted into the market novel nutraceutical or health supplements for therapeutic or prophylactic intervention based on the consumption of mono-specific or mixed IgY formulations. With recent trends in consumer preference for natural materials to alleviate health concerns, the increasing healthcare costs and the recent advances in drug delivery systems, IgY is likely to shift from its mainly functional food status toward pharmaceuticalization in the foreseeable future.

Keywords: antibody; functional food; health management; human; immunoglobulin; immunotherapy; passive; veterinary.

Figure 1. Basic structure of IgY. IgY molecule containing two heavy and two light chains. The heavy chain consists of a variable domain (VH) and four constant domains (CH1, CH2, CH3 and CH4). The two heavy chains are connected by disulfide bonds are shown as solid (known) or dashed (putative) lines. The light chain has one variable domain (VL) and only one constant domain (CL). Fragment antibody (Fab) domain binds to antigenic epitopes, Fragment crystallizable (Fc) domain of IgY has biological effector functions, are circled. The domain structure of IgG shown here with the hinge region represented by a zigzag line linking CH1 and CH2.

Figure 2. Effect of heat, pH and pepsin on IgY-Hp. IgY-Hp was treated at various temperatures for 10 min (A), at various pHs for 4 h (B) and with pepsin (15 ml/ml) (C) at pH 2, 4 and 6 for 0.5, 1, 2 and 4 h. Remaining activities after the treatments were measured using ELISA and are expressed as a percentage of the initial activity. Adapted with permission from Shin et al.

Figure 3. In vitro IgY release from IgY loaded microcapsules. Samples were first incubated in stimulated gastric fluid for 2 h, and then transferred to stimulated intestinal fluid for 4 h. The accumulative release percentages was calculated by equation Data are presented as mean SD (n = 3). Adapted with permission from Li et al.

Figure 4. In vivo passage of IgY in the gastrointestinal tract of calves. Anti-K99 fimbriae antibody titers of IgY in the gastrointestinal tract of calves after 2, 6 and 24 h post administration. Adapted with permission from Ikemori et al.

Figure 5. Effect of Anti-gingipain IgY on clinical parameters in the periodontitis patients: (A) Bleeding On Probe (BOP) (B) Probing Depth (PD) (C) P. gingivalis rate (P. gingivalis/Total) (%). Adapted with permission from Yokoyama et al.

Figure 6. Effect of Anti-CA IgY on growth of C. albicans in saliva in volunteer study. B1 = Before treatment; T1 = First time treatment; A1 = Stop treatment after T1; T2 = Second time treatment; A2 = Stop treatment after T2; T3 = Third time treatment. Adapted with permission from Ibrahim et al.

Figure 7. Effect of Anti-HP IgY on Average value of: (A) UBT (carbon urea breath test) and (B) Stool antigen detection in volunteer study. Adapted with permission from Yamane et al.

Figure 8. Effect of Rotamix IgY on daily frequency of rotavirus shedding in stools of children. *Significant differences between Rotamix IgY and placebo IgY groups (*p ≤ 0.05, chi-square test). Adapted with permission from Rahman et al.