Prophylaxis of rotavirus gastroenteritis using immunoglobulin

Oral inoculation of the human group A rotavirus MO strain (G serotype 3) into 5-day-old BALB/c mice causes gastroenteritis characterized by diarrhea. Using this small animal model, passive protection of suckling mice against human rotavirus infection was

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VIrology

Arch Virol (1996) [Suppl] 12: 217-223

© Springer-Verlag 1996

Prophylaxis of rotavirus gastroenteritis using immunoglobulin T. Ebina Division of Immunology, Research Institute Miyagi Cancer Center, Natori, Miyagi, Japan

Summary. Oral inoculation of the human group A rotavirus MO strain (G serotype 3) into 5-day-old BALB/c mice causes gastroenteritis characterized by diarrhea. Using this small animal model, passive protection of suckling mice against human rotavirus infection was achieved with the use of immunoglobulin (IgY) from the yolks of eggs of rota virus-immunized hens. When Ig Y against the rotavirus strain homotypic with the challenge virus (MO strain) was administered to mice, complete protection was achieved. After immunizing 8-month old pregnant Holstein cows with human rotavirus MO strain, colostrum containing neutralizing antibody to four different G serotypes of human rotavirus, designated Rota colostrum, was obtained. Rota colostrum completely protected suckling mice against rotavirus infection, and purified IgG obtained from Rota colostrum protected against infection with the homologous virus. After randomly grouping 20 infants from a baby care center, 10 infants received 20 ml of Rota colostrum for 2 weeks and 10 control infants received none. Rotavirus-associated diarrhea developed in 7 of the 10 infants in the control group. None of the three infants in the group daily receiving the Rota colostrum had such symptoms, and one of three infants in the group receiving treatment, every other day developed rota virus-induced diarrhea. Oral administration of Rota colostrum seems to be an effective and safe means of preventing diarrhea caused by human rotavirus infection. Recently, the immunized cows were boosted by reinjection of 4 serotypes of human rotavirus into a superficial cervical lymph node two weeks after delivery, resulting in mass production of cow's milk containing a hightitered antibody to human rotavirus. Therefore, the hyperimmune cow's milk is a candidate for a "physiologically functional food" in Japan. Introduction Group A rotaviruses were first recognized in 1973 as causes of infectious gastroenteritis in infants and are now known to be the leading cause of severe diarrhea in infants and young children throughout the world. Vaccine development is in progress, but difficulty has emerged in obtaining sufficiently broad protection against disease caused by the several human rotavirus VP7 (G)

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serotypes. The principal failure of vaccine candidates in field trials has been due to the limited immune response elicited in mucosal regions where rotavirus infections occur. The most important protection factor against the development of rota virus diarrhea is the presence of specific antibody in the lumen of the small intestine. In order to analyze the precise mechanism by which rotavirus-induced gastroenteritis can be prevented with immunoglobulins, we needed a small animal model of experimental infection initiated by a human rotavirus. We have succeeded in inducing t