Rotaviruses are consistently shown to be the sungle most important etiologic agents of severe diarrhea of infants and young children world-wide. We are engaged in studies to develop a human rotavirus vaccine with the goal of preventing or modifying the severe toll resulting from rotavirus illness; it is estimated that 873,000 infants and young children under five years of age die from rotavirus diarrhea annually in the developing countries of the world (Institute of Medicine Report). Our current vaccination strategy is comprised of the use of an animal rotavirus strain (derived from a rhesus monkey) in combination with three human rotavirus-rhesus rotavirus reassortant strains to form a quadrivalent vaccine in an attempt to achieve protection against each of the four epidemiologically important rotavirus serotypes. This """"""""Jennerian"""""""" and """"""""modified Jennerian"""""""" approach to vaccination has met with variable success in field trials and is continuing to be evaluated. We are now considering the use of a cold-adapted human rotavirus strain(s) as a candidate vaccine because it may yield a higher degree of protection than the aforementioned vaccine, because the cold-adapted strain(s) possess the human rotavirus VP4 (whereas the quadrivalent vaccine possesses the rhesus rotavirus VP4), an important outer capsid protein that may be important in the induction of heterotypic immunity. VP4 is one of two outer capsid rotavirus proteins associated with protection against rotavirus disease in animal models. In order to determine if the cold-adapted human rotavirus strain is attenuated, an important first step is the development of a suitable animal model is needed that can be reproducibly infected and can develop diarrhea following administration of a virulent human rotavirus strain by the alimentary route. Therefore, we administered a serotype 1 human rotavirus strain (that was known to be virulent in prior studies in adult human volunteers) to two chimpanzees by the alimentary route via gastric tube; one of them: (1) developed loose stools on the fourth, fifth, and sixth days after inoculation; (2) shed rotavirus on day 2 to at least day 7; and (3) developed a seroresponse to the serotype 1 virus by plaque reduction neutralization (PRN) assay. The other chimpanzee developed loose stools beginning on the third or fourth day and subsiding before the fifth day after inoculation. The latter animal did not shed rotavirus and failed to develop a seroresponse to serotype 1 rotavirus by PRN assay.
