Vaccines are beneficial and universal tools to prevent
infectious disease. Thus, safety of
vaccines is strictly evaluated in the preclinical phase of trials and every
vaccine batch must be tested by the National Control Laboratories according to the guidelines published by each country. Despite many
vaccine production platforms and methods, animal testing for safety evaluation is unchanged thus far. We recently developed a systems biological approach to
vaccine safety evaluation where identification of specific
biomarkers in a rat pre-clinical study evaluated the safety of
vaccines for pandemic H5N1
influenza including Irf7, Lgals9, Lgalsbp3, Cxcl11, Timp1, Tap2, Psmb9, Psme1, Tapbp, C2, Csf1, Mx2, Zbp1, Ifrd1, Trafd1, Cxcl9, β2m, Npc1, Ngfr and Ifi47. The current study evaluated whether these 20
biomarkers could evaluate the safety, batch-to-batch and manufacturer-to-manufacturer consistency of seasonal
trivalent influenza vaccine using a multiplex gene detection system. When we evaluated the
influenza HA
vaccine (HAv) from four different manufactures, the
biomarker analysis correlated to findings from conventional animal use tests, such as abnormal toxicity test. In addition, sensitivity of toxicity detection and differences in HAvs were higher and more accurate than with conventional methods. Despite a slight decrease in
body weight caused by HAv from manufacturer B that was not statistically significant, our results suggest that HAv from manufacturer B is significantly different than the other HAvs tested with regard to Lgals3bp, Tapbp, Lgals9, Irf7 and C2 gene expression in rat lungs. Using the
biomarkers confirmed in this study, we predicted batch-to-batch consistency and safety of
influenza vaccines within 2 days compared with the conventional safety test, which takes longer. These
biomarkers will facilitate the future development of new
influenza vaccines and provide an opportunity to develop in vitro methods of evaluating batch-to-batch consistency and
vaccine safety as an alternative to animal testing.