IgY Antibodies Protect against Human Rotavirus Induced Diarrhea in the Neonatal Gnotobiotic Piglet Disease Model

Abstract

Group A Rotaviruses are the most common cause of severe, dehydrating diarrhea in children worldwide. The aim of the present work was to evaluate protection against rotavirus (RV) diarrhea conferred by the prophylactic administration of specific IgY antibodies (Ab) to gnotobiotic piglets experimentally inoculated with virulent Wa G1P[8] human rotavirus (HRV). Chicken egg yolk IgY Ab generated from Wa HRV hyperimmunized hens specifically recognized (ELISA) and neutralized Wa HRV in vitro. Supplementation of the RV Ab free cow milk diet with Wa HRV-specific egg yolk IgY Ab at a final ELISA Ab titer of 4096 (virus neutralization –VN- titer = 256) for 9 days conferred full protection against Wa HRV associated diarrhea and significantly reduced virus shedding. This protection was dose-dependent. The oral administration of semi-purified passive IgY Abs from chickens did not affect the isotype profile of the pig Ab secreting cell (ASC) responses to Wa HRV infection, but it was associated with significantly fewer numbers of HRV–specific IgA ASC in the duodenum. We further analyzed the pigś immune responses to the passive IgY treatment. The oral administration of IgY Abs induced IgG Ab responses to chicken IgY in serum and local IgA and IgG Ab responses to IgY in the intestinal contents of neonatal piglets in a dose dependent manner. To our knowledge, this is the first study to show that IgY Abs administered orally as a milk supplement passively protect neonatal pigs against an enteric viral pathogen (HRV). Piglets are an animal model with a gastrointestinal physiology and an immune system that closely mimic human infants. This strategy can be scaled-up to inexpensively produce large amounts of polyclonal IgY Abs from egg yolks to be applied as a preventive and therapeutic passive Ab treatment to control RV diarrhea.

Reduction of aGVHD using chicken antibodies directed against intestinal pathogens in a murine model

“…Our findings are in line with previous studies demonstrating that administration of IgY leads to reduction of the viral load. 15,16 The exact mechanisms remain unknown; so far, however, several mechanisms have been proposed in earlier publications, including agglutination, opsonization, and toxin neutralization. 17,18 Furthermore, previous studies revealed a correlation between high organ damage, population shift toward E coli, and the abundance of adherent-invasive E coli in patients with Crohn disease compared with healthy subjects.…”

Recombinant Monovalent Llama-Derived Antibody Fragments (VHH) to Rotavirus VP6 Protect Neonatal Gnotobiotic Piglets against Human Rotavirus-Induced Diarrhea

“…Similar studies that used passive IgA monoclonal Abs to VP6 suggested that protection in vivo is in fact mediated by the binding of VP6 IgA Ab to RVA, which protects by intracellular neutralization during transcytosis in the mouse gut [44], [48]–[50]. In any case, it is well known that the continuous presence of high titers of passive RVA Abs in the gut lumen (naturally produced or artificially added to the milk) fully protects against diarrhea and significantly reduces virus shedding [43], [51]–[53]. We have previously developed VHH against VP6 from bovine RVA strain C486 (G6P[1]I?).…”

Rotavirus VP6 preparations as a non-replicating vaccine candidates

“…To support these results, generated VHH molecules directed VP6 in insect cells indicate the same functionality as those expressed in E. coli inducing a broad neutralization activity in vitro and protection against diarrhea and RV shedding in a neonatal mouse model [114]. It has also been shown that the VHH nanoAb can block the infection independently of the RV strain genotypes in vitro and observed a high protection against RV Wa strain in gnotobiotic pigs in vivo [115] as well as VP6-specific IgY Abs from egg yolk [116]. However, DLP2/6 was found to induce neither neutralizing Ab titer nor protecting neonatal Gnotobiotic Piglets against RV challenge [117].…”