Laboratory and clinical studies have been directed toward development of a vaccine against rotavirus gastroenteritis in infants. First, bovine rotavirus strain WC3, which did not induce neutralizing antibodies to predominant human rotavirus (HRV) serotypes, was determined to be safe and immunogenic; however, it was not protective in all efficacy trials. HRVs adapted to cell culture retained some virulence for infants, but when further attenuated by cold adaptation, they were poorly immunogenic. Reassortant rotaviruses were designed to express HRV surface proteins VP7 (G) or VP4 (P) while retaining a bovine WC3 genome background. Reassortants containing either HRV surface protein and as few as four bovine rotavirus genes were safe in infants. A monovalent WC3 reassortant of serotype G1 specificity was 64%-100% protective in placebo-controlled trials. A quadrivalent WC3 reassortant vaccine with components of HRV G1, G2, G3, and P[8] specificity induced 67% protection against all rotavirus disease in a multicenter efficacy trial.
Simian rotavirus SAil was shown to replicate in the gastrointestinal tracts of infant mice after oral inoculation. Clinical symptoms, histopathological changes in the small intestinal mucosa, and the type-specific humoral immune response were all characteristic of rotavirus-induced gastroenteritis. The availability of this small animal model for the study of a primate rotavirus infection should expedite analysis of the immune response necessary for protection against challenge.
Proloneed unex~lained fever is a continuine ~roblem in a s s o c i a t e d w i t h s i g n i f i c a n t m o r b i d i t y and m o r t a l i t y f o r very low b i r t h w e i g h t (LBW) i n f a n t s , <1300gm, and i n f a n t-t o-i n f a n t t r a n s m i s s i o n h a s a p p a r e n t l y occurred.
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