Laboratory Animals > Volume 43, Number 2 > Pp. 155-164

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Reducing variation in a rabbit vaccine safety study with particular emphasis on housing conditions and handling

Cynthia M Verwer ¹ , Arno van der Ark ², Geert van Amerongen ³, Ruud van den Bos ¹ and Coenraad F M Hendriksen ^1 3

¹ Department of Animals, Science and Society, Utrecht University, PO Box 80.166, 3508 TD Utrecht; ² Department of Product and Process Development, Netherlands Vaccine Institute (NVI); ³ Joint Centre for Laboratory Animals Studies, NVI, PO Box 457, 3720 AL, Bilthoven, The Netherlands

Corresponding author: Cynthia M Verwer. Email: cmverwer{at}yahoo.com

This paper describes the results of a study of the effects of modified housing conditions, conditioning and habituation on humans using a rabbit model for monitoring whole-cell pertussis vaccine (pWCV)-induced adverse effects. The study has been performed with reference to previous vaccine safety studies of pWCV in rabbits in which results were difficult to interpret due to the large variation in experimental outcome, especially in the key parameter deep-body temperature (T_b). Certain stressful laboratory conditions, as well as procedures involving humans, e.g. blood sampling, inoculation and cage-cleaning, were hypothesized to cause this large variation. The results of this study show that under modified housing conditions rabbits have normal circadian body temperatures. This allowed discrimination of pWCV-induced adverse effects in which handled rabbits tended to show a dose-related increase in temperature after inoculation with little variance, whereas non-handled rabbits did not. Effects of experimental and routine procedures on body temperature were significantly reduced under modified conditions and were within the normal T_b range. Handled animals reacted less strongly and with less variance to experimental procedures, such as blood sampling, injection and cage-cleaning, than non-handled rabbits. Overall, handling had a positive effect on the behaviour of the animals. Data show that the housing modifications have provided a more robust model for monitoring pWCV adverse effects. Furthermore, conditioning and habituation of rabbits to humans reduce the variation in experimental outcome, which might allow for a reduction in the number of animals used. In addition, this also reduces distress and thus contributes to refining this animal model.

Key Words: Rabbit • housing conditions • handling • body temperature • pertussis whole-cell vaccine • reduction • refinement

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