Rotaviruses are an important cause of diarrhea with significant morbidity in several vertebrate species including cattle, swine, horses, mice and humans. Previous studies suggest that antibody must be present within the intestinal lumen to prevent rotavirus diarrhea. Unfortunately, rotaviruses are difficult to adapt to cell culture and to attenuate; thus, the development of live vaccines capable of producing a protective intestinal immune response has been impeded. An alternative to active immunoprophylaxis involves the local protection of the intestine by oral administration of colostrum, serum immunoglobulins or other factors. These materials may also be of benefit in the treatment of rotaviral disease.
The specific aims of the proposed study are: (1) to identify and characterize serum or milk factors which can be administered orally to provide local protection against gastroenteritis caused by viruses such as rotavirus, (2) to characterize the effects of orally administered protective factors on rotavirus infection and on the short and long term immune response to rotavirus, and (3) to determine the pharmacokinetics of the orally administered protective factors. Murine rotavirus, epizootic diarrhea of infant mice, will be used as the experimental model. Isolated serum or milk factors will be orally administered to seronegative suckling mice. The mice will then be inoculated with murine rotavirus. Rotaviral disease will be assessed by gross and microscopic pathology. Infection will be monitored by immunofluorescence of intestinal sections and by enzyme immunoassay of intestinal suspensions. Rotaviral immunity will be characterized by enzyme immunoassay of sera and intestinal samples. The pharmacokinetics of the orally administered protective factors will be determined using radioactive and biotin labeled factors. The information gained from this study, as well as the research techniques to be learned, have broad applicability to rotavirus infections in laboratory animals, domestic animals and humans. Additionally, the use of orally administered factors in the prevention and treatment of intestinal disease has practical implications, not only for rotaviruses, but also for other localized viral intestinal diseases such as coronavirus, parvovirus and adenovirus infections which are of importance in both animals and humans.
