Predictive models and correlates of protection for testing biodefence vaccines.

The identification of immune correlates of protection is becoming increasingly important in order to derive a quantitative assessment of the benefit conferred by vaccination in clinical trials. The use of immune correlates of protection as an indirect measure of clinical efficacy is essential to achieve regulatory approval for vaccines for which clinical efficacy cannot be tested directly, for example, biodefence vaccines. The correlates apply to the specific vaccine formulation being developed; in general, if a statistically significant correlation is found between a measurable immunological readout and survival in authentic animal models of human infection, the same immunological readout can be defined and applied as a surrogate marker of protection in clinical studies. The surrogate markers of protection can then be used to predict the protective efficacy of a candidate vaccine in humans. This review summarizes some of the immune correlates data reported for biodefence vaccines as well as some of the analytical approaches that can be applied in order to predict clinical efficacy.