**10. Extrapolation of the safety evaluation results to humans according to biomarkers' gene function**

Given that the evaluation of the quality and safety of vaccines assumes a reaction with humans, the evaluation result must reflect the human biological response. Generally, there are species differences in immunological responses between humans and rodents. Therefore, it is necessary to interpret the results carefully.

In case of safety evaluations based on genomic analyses, estimating the difference between experimental animals and humans with reference to the function of genes may be partially possible. For example, in the case of the WPV, leukopenic toxicity and body weight loss are observed in rodents, but these effects cannot be verified in humans. Nevertheless, at the gene level, if a gene is conserved among species, it is possible to estimate whether similar biological reactions can be observed between humans and animals. All our identified marker genes are homologous to their human counterparts, except for *Ifi47*. This observation suggests that some phenomena common to the tested animals and humans may be identified via the animal experiments by means of marker genes. To test this hypothesis and to develop an *in vitro* assay system, the use of human peripheral blood mononuclear cell-based or alveolar-epithelial-cell-based methods is necessary. Thus, extrapolation of the results of these evaluations to humans can be partially achieved by bridging the species differences with the marker genes.
