Large-Animal Model for Establishing E/T Ratio of Adjuvants

  • Luuk A. Th. HilgersEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 626)


To develop novel adjuvants for use in humans, the efficacy/toxicity (E/T) ratio of experimental products in large animal species can be investigated. The test model included two intramuscular immunizations in pigs at 3 weeks interval and analysis of immune responses and local reactions 1 week after the second injection. The antigen used to determine adjuvant activity was a well-defined, purified, viral glycoprotein that without adjuvant induces low immune responses and no detectable local reactions. Efficacy was determined by measuring ELISA and virus-neutralizing antibody titres. Toxicity was determined by necropsy and estimating size and severity of local reactions to each treatment. The persistence of the side effects was deduced from the difference in the local reaction 4 weeks after the first and 1 week after the second injection. For graphic representation of E/T ratios, toxicity was expressed in arbitrary units and plotted against antibody titre. The graphs provided insight into dose– and structure–response relationships and enabled the stepwise optimization of adjuvant candidates.

Key words

Animal model pig efficacy local toxicity reactogenicity E/T ratio necropsy risk/benefit ratio 


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Nobilon International BVBoxmeerthe Netherlands

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