Response of colostrum-deprived cynomolgus monkeys to intragastric challenge exposure with simian rotavirus strain SA11

Bryon W. Petschow From the Mead Johnson Research Center (Petschow, Litov), Bristol-Myers Squibb Co, 2400 W. Lloyd Expressway, Evansville, IN 47721; California Primate Research Center (McGraw), and the Department of Pathology (Young), School of Medicine, University of California, Davis, CA 95616.

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Richard E. Litov From the Mead Johnson Research Center (Petschow, Litov), Bristol-Myers Squibb Co, 2400 W. Lloyd Expressway, Evansville, IN 47721; California Primate Research Center (McGraw), and the Department of Pathology (Young), School of Medicine, University of California, Davis, CA 95616.

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Lawrence J. T. Young From the Mead Johnson Research Center (Petschow, Litov), Bristol-Myers Squibb Co, 2400 W. Lloyd Expressway, Evansville, IN 47721; California Primate Research Center (McGraw), and the Department of Pathology (Young), School of Medicine, University of California, Davis, CA 95616.

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Thomas P. McGraw From the Mead Johnson Research Center (Petschow, Litov), Bristol-Myers Squibb Co, 2400 W. Lloyd Expressway, Evansville, IN 47721; California Primate Research Center (McGraw), and the Department of Pathology (Young), School of Medicine, University of California, Davis, CA 95616.

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Summary

The infectivity and pathogenic potential of a cell culture-adapted simian rotavirus was evaluated in colostrum-deprived newborn and infant cynomolgus macaques (Macaca fascicularis). Intragastric challenge exposure with the simian rotavirus strain SA11 on postpartum day 2 induced diarrhea in 5 of 5 colostrum-deprived newborn monkeys. Compared with sham-inoculated controls, 3 of the 5 inoculated monkeys also manifested reduced body weight gain during the initial 5 days after challenge exposure. Rotavirus was detected in feces of 3 challenge-exposed monkeys for up to 2 days after inoculation. Evaluation of antibody response after rotavirus inoculation was obscured by high but variable prechallenge-exposure serum titers of rotavirus-specific antibody. Preexisting serum titer of neutralizing antibody in newborn monkeys was not predictive of clinical response to inoculation with rotavirus SA11. Two 90-day-old infant monkeys with low serum neutralizing antibody titer did not have diarrhea, reduced weight gain, or antibody response after oral inoculation with rotavirus SA11. Results of these challenge-exposure studies in newborn cynomolgus monkeys were consistent with a heterologous host-rotavirus model and indicate that neonatal serum antibody of maternal origin may not be associated with resistance to rotavirus-induced disease.

Summary

The infectivity and pathogenic potential of a cell culture-adapted simian rotavirus was evaluated in colostrum-deprived newborn and infant cynomolgus macaques (Macaca fascicularis). Intragastric challenge exposure with the simian rotavirus strain SA11 on postpartum day 2 induced diarrhea in 5 of 5 colostrum-deprived newborn monkeys. Compared with sham-inoculated controls, 3 of the 5 inoculated monkeys also manifested reduced body weight gain during the initial 5 days after challenge exposure. Rotavirus was detected in feces of 3 challenge-exposed monkeys for up to 2 days after inoculation. Evaluation of antibody response after rotavirus inoculation was obscured by high but variable prechallenge-exposure serum titers of rotavirus-specific antibody. Preexisting serum titer of neutralizing antibody in newborn monkeys was not predictive of clinical response to inoculation with rotavirus SA11. Two 90-day-old infant monkeys with low serum neutralizing antibody titer did not have diarrhea, reduced weight gain, or antibody response after oral inoculation with rotavirus SA11. Results of these challenge-exposure studies in newborn cynomolgus monkeys were consistent with a heterologous host-rotavirus model and indicate that neonatal serum antibody of maternal origin may not be associated with resistance to rotavirus-induced disease.

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