Pigs in Gp5 and Gp6 (Wa HRV IgG 4096 dairy and Ab free milk, respectively) were negative for Abs to IgY (Figure 4). == The oral administration of semi-purified passive heterologous IgY Abs did not affect the isotype profile of the Ab secreting cell responses to Vir Wa HRV infection but was associated with significantly fewer numbers of HRVspecific IgA ASC in the duodenum == Antibody secreting cell (ASC) responses to Wa HRV at 21 PID were mainly distributed along the different portions of the intestinal lamina propria (duodenum, jejunum and ileum), followed by the mesenteric lymph nodes. 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 SB269970 HCl are an animal model with a gastrointestinal physiology and an immune system that SB269970 HCl 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. == Introduction == Group A rotaviruses SB269970 HCl (RVA) are the most common cause of severe, dehydrating diarrhea in children worldwide. Diarrhea causes 1.3 million deaths in children younger than 5 years annually[1],[2]. Rotavirus surveillance studies indicate that all young children experience at least one RVA infection by 5 years of age[3],[4]. Moreover, RV infection is responsible for about 30% of all hospital admissions for diarrheal disease and causes an estimated of 400,000600,000 deaths per year among children worldwide[5]. Most of these deaths occur in developing countries in Asia and sub-Saharan Africa, where human (H) RV is the leading cause of life-threatening diarrhea in infants and young children[3],[4]. The National Rotavirus Surveillance Program reported almost 120,000 cases of diarrhea and 150 deaths associated with RV in children under 5 years old in Argentina[6]. The five most prevalent G (VP7) and P (VP4) genotypes worldwide include G1, G3, G4, and G9 with P[8] and G2 P[4][7]. The virus infects the mature villus epithelial SB269970 HCl cells of the small intestine and infection Rabbit Polyclonal to OGFR often leads to fever, vomiting and diarrhea in children. Dehydration and electrolyte disturbances are the major sequelae of HRV infection and occur most often in the youngest children[8],[9]. The high morbidity and mortality related with HRV gastroenteritis makes its prevention and treatment an important public-health goal. A specific, effective and affordable therapy is currently not available[10]. However, two RVA vaccines were licensed in 2006. Rotarix is a monovalent live attenuated vaccine derived from the most common circulating wild-type strain G1P[8] (Glaxo SmithKline Biologicals, Belgium) and RotaTeq is composed of 5 RV strains, each of which is a single-gene reassortant based on a parent bovine strain -WC3- that contains an outer capsid gene from a human strain that induces immunity to the most common genotypes of HRV in circulation G1 to G4 and P1A[8](Merck & Co., USA). Both vaccines were efficacious in preventing severe gastroenteritis, predominantly due to the G1 HRV serotype[8],[11],[12], in developed countries. However in children from developing countries, the efficacy rates were lower[13]. There is also evidence of vaccine-acquired RVA infection in children with severe combined immunodeficiency[14]. Studies of candidate vaccines, passive antibody (Ab) treatments and development of immune responses to HRV can be conducted in the neonatal gnotobiotic (Gn) pig model, the only animal model susceptible to HRV infection and disease[15],[16]. Furthermore, the gastrointestinal physiology and immune system of the neonatal Gn piglets resemble those of human infants, so responses detected in neonatal pigs closely mimic those observed after natural HRV infection of infants in terms of the pathogenicity of HRV challenge[15],[17]. The animals are colostrum-deprived, maintained in isolator units and fed sterile milk, assuring a pathogen/microbe-free and Ab-free status, making them an ideal model to study active or passive immunityin vivo[15],[16],[18],[19],[20],[21]. Regarding the immune correlates of protection from RVA infection and disease it is now known that both humoral and cell-mediated.