Can in vitro methods reliably replace existing vaccine challenge tests?

Abstract

The OIE Terrestrial Manual and the European Pharmacopoeia (EP) still describe live challenge experiments for FMDV vaccine potency tests. However, the EP allows for other validated tests and specifically in vitro tests if a “satisfactory pass level” has been determined. Much research is now focused on validating the replacement of live challenge with in vitro tests. Three issues have to be resolved first: the definition of a satisfactory vaccine; a record of the effectiveness of existing live challenge tests; and a validation of new tests to show that they can safely replace the old ones. This paper looks at all three issues. It describes a metric, based on vaccine potency requirements, against which tests can be measured; we then characterise existing tests, and recommend that these be the minimum standard for a replacement in vitro test; finally, we propose using this same metric to validate such a test.