A gastrointestinal rotavirus infection mouse model for immune modulation studies
Background
Rotaviruses are the single most important cause of severe diarrhea in young children worldwide. The current study was conducted to assess whether colostrum containing rotavirus-specific antibodies (Gastrogard-R®) could protect against rotavirus infection. In addition, this illness model was used to study modulatory effects of intervention on several immune parameters after re-infection.
Methods
BALB/c mice were treated by gavage once daily with Gastrogard-R® from the age of 4 to 10 days, and were inoculated with rhesus rotavirus (RRV) at 7 days of age. A secondary inoculation with epizootic-diarrhea infant-mouse (EDIM) virus was administered at 17 days of age. Disease symptoms were scored daily and viral shedding was measured in fecal samples during the post-inoculation periods. Rotavirus-specific IgM, IgG and IgG subclasses in serum, T cell proliferation and rotavirus-specific delayed-type hypersensitivity (DTH) responses were also measured.
Results
Primary inoculation with RRV induced a mild but consistent level of diarrhea during 3-4 days post-inoculation. All mice receiving Gastrogard-R® were 100% protected against rotavirus-induced diarrhea. Mice receiving both RRV and EDIM inoculation had a lower faecal-viral load following EDIM inoculation then mice receiving EDIM alone or Gastrogard-R®. Mice receiving Gastrogard-R® however displayed an enhanced rotavirus-specific T-cell proliferation whereas rotavirus-specific antibody subtypes were not affected.
Conclusions
Preventing RRV-induced diarrhea by Gastrogard-R® early in life showed a diminished protection against EDIM re-infection, but a rotavirus-specific immune response was developed including both B cell and T cell responses. In general, this intervention model can be used for studying clinical symptoms as well as the immune responses required for protection against viral re-infection.
Background
Rotavirus is one of the leading causes of severe dehydrating diarrhea in children under the age of five and causes the deaths of >600,000 children annually. Rotaviruses, belonging to a genus of double-stranded RNA viruses in the family Reoviridae, infect the mature villus epithelial cells of the small intestine, often leading to fever, vomiting, and diarrhea in children. Current treatment is non-specific and consists mainly of oral rehydration therapy to prevent dehydration. Two live-attenuated vaccines have been licensed recently and have so far proven safe and efficacious. However, previous experience with the first licensed rotavirus vaccine, which was withdrawn from the market a year after introduction due to a possible correlation between vaccine application and the occurrence of intussusceptions, has reinforced the need to develop alternative approaches to control rotavirus disease. Fundamental to this development is a better insight of the immune responses related to gastrointestinal virus infections which will help to develop improved treatment and/or preventive regimes.