Early Oral Ovalbumin Exposure during Maternal Milk Feeding Prevents Spontaneous Allergic Sensitization in Allergy-Prone Rat Pups

El-Merhibi, Adaweyah; Lymn, Kerry A.; Kanter, Irene; Penttila, Irmeli A.

doi:10.1155/2012/396232

Cited by 4 publications

(5 citation statements)

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“…When the antigen was changed from OVA to the readily absorbable human gamma globulins (HGG; 1 mg/g), the mice developed tolerance [38] but they developed an immune response if HGG dose was reduced to 0.1 µg/g. Penttila et al (2012) fed rat pups 1 mg OVA intermittently or daily from day 4 after birth until day 13 [39]. Regardless of the dosing regimen, they determined that dam-reared pups produced low levels of circulating OVA-specific IgE and IgG1 and they suggest that early daily OVA exposure may prevent early allergic sensitization [39].…”

Section: Resultsmentioning

confidence: 99%

“…Penttila et al (2012) fed rat pups 1 mg OVA intermittently or daily from day 4 after birth until day 13 [39]. Regardless of the dosing regimen, they determined that dam-reared pups produced low levels of circulating OVA-specific IgE and IgG1 and they suggest that early daily OVA exposure may prevent early allergic sensitization [39]. These data are in excellent agreement with our preliminary work which showed that pups fed 1 mg OVA or higher for up to 2 weeks responded with oral tolerance (referred to in Section 3.1).…”

Section: Resultsmentioning

confidence: 99%

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Low Dose Antigen Exposure for a Finite Period in Newborn Rats Prevents Induction of Mucosal Tolerance

2012

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BackgroundIn adult rats, initial exposure to antigens by a mucosal route triggers tolerance such that any subsequent re-exposure, even by a systemic route, results in suppression of immunity. The newborn’s gut is semi-permeable for a finite period to allow maternal antibodies to enter the newborn’s circulation. We propose that antigens introduced in extreme early life can readily traverse the gut wall and therefore circumvent induction of mucosal tolerance.Methodology/Principle FindingsRat pups were gavaged with low-doses of ovalbumin (OVA; oral exposure group) or saline (parenteral control group) every second day for several weeks followed by an intraperitoneal (i.p.) injection at 1 month of age. When gavage was initiated the day after birth, newborn oral exposure pups responded with significantly higher anti-OVA IgA, IgM, IgG2a, and IgG1 titres in their serum and anti-OVA IgA, IgG2a and IgG1 titres in their lungs compared to negative control pups. Oral exposure alone failed to induce immunity. Pups exposed to the same treatment regimen starting at 14 days of age showed induction of mucosal tolerance after i.p. immunization. Newborn oral exposure groups subjected to secondary i.p. immunization responded with significantly increased humoral immunity in lung and sera suggesting that once antigen-specific mucosal tolerance if circumvented, it persists. Lymphocytes derived from mesenteric lymph node cells re-simulated with OVA ex vivo, from newborn oral exposure pups exposed to secondary immunization produced significantly higher IFN-γ expression and lymphocyte proliferation relative to control pups indicating prevention of tolerance in the cell-mediated immune system.Conclusions/SignificanceThis work demonstrates that newborns may be uniquely qualified to prevent induction of mucosal tolerance to oral antigens. These results should be further explored to establish whether prevention of tolerance by early life oral vaccination can be exploited to prime for mucosal as well as systemic immunity and thus protect this susceptible population against infectious diseases.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Low Dose Antigen Exposure for a Finite Period in Newborn Rats Prevents Induction of Mucosal Tolerance

2012

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“…However, because of the high morbidity and mortality of HRV associated diarrhea in developing countries and among immunesuppressed patients, the potential risk of sensitizing these patients to egg during infancy or an episode of frequently fatal gastroenteritis must be balanced against their potential benefit as determined by appropriate clinical trials [61] . Alternatively, the administration of chicken IgY Abs to breast fed children may be of less concern, since important immune molecules such as TGF-β present in human maternal milk has been shown to be a strong anti-allergenic factor inducing oral tolerance to dietary antigens in neonates [62] . Finally, IgY Abs have been used in randomized, placebo-controlled clinical trials carried out by Sarker et al and by Rahman et al in hospitalized children.…”

Section: Discussionmentioning

confidence: 99%

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

Vega¹,

Bok²,

Vlasova

et al. 2012

PLoS ONE

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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.

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“…Although several dietary interventions in this model have shown their immunomodulatory activity in young-adult animals [ 121 ], very few studies have focused on earlier periods of life [ 122 ]. For example, this rat strain is also suitable for studying how diet can modulate spontaneous allergic sensitization when the early oral allergen exposure is performed during maternal milk feeding [ 123 ]. Therefore, this model can also be used to ascertain the dietary modulation of the development of oral tolerance in early life.…”

Section: Immunomediated Pathologies In Early Rat Lifementioning

confidence: 99%

The Suckling Rat as a Model for Immunonutrition Studies in Early Life

Pérez-Cano

Franch

Castellote

et al. 2012

Clinical and Developmental Immunology

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Diet plays a crucial role in maintaining optimal immune function. Research demonstrates the immunomodulatory properties and mechanisms of particular nutrients; however, these aspects are studied less in early life, when diet may exert an important role in the immune development of the neonate. Besides the limited data from epidemiological and human interventional trials in early life, animal models hold the key to increase the current knowledge about this interaction in this particular period. This paper reports the potential of the suckling rat as a model for immunonutrition studies in early life. In particular, it describes the main changes in the systemic and mucosal immune system development during rat suckling and allows some of these elements to be established as target biomarkers for studying the influence of particular nutrients. Different approaches to evaluate these immune effects, including the manipulation of the maternal diet during gestation and/or lactation or feeding the nutrient directly to the pups, are also described in detail. In summary, this paper provides investigators with useful tools for better designing experimental approaches focused on nutrition in early life for programming and immune development by using the suckling rat as a model.

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Early Oral Ovalbumin Exposure during Maternal Milk Feeding Prevents Spontaneous Allergic Sensitization in Allergy-Prone Rat Pups

Cited by 4 publications

References 59 publications

Low Dose Antigen Exposure for a Finite Period in Newborn Rats Prevents Induction of Mucosal Tolerance

Low Dose Antigen Exposure for a Finite Period in Newborn Rats Prevents Induction of Mucosal Tolerance

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

The Suckling Rat as a Model for Immunonutrition Studies in Early Life

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