Establishment of minimal positive-control conditions to ensure brain safety during rapid development of emergency vaccines

Baek, Hyekyung; Kim, Kwang Ho; Park, Min Young; Kim, Kyeongryun; Ko, Bokyeong; Seo, Hyung Seok; Kim, Byoung Soo; Hahn, Tae-Wook; Yi, Sun Shin

After considering the study's results, we have established a positive-control protocol for verification of vaccine safety to brain by measuring BBB disruption and restoration conditions via a molecular biological approach. We conclude that the ICR mouse strain is suitable for use in the protocol with TJ disruption of the BBB assessed after 4 h of exposure following systemic LPS administration at a dosage of 1 mg LPS(S) in 4 mL PBS per kilogram body weight. By comparing the TJ mRNA levels at 4 h PI between the LPS-injected group and the selected vaccine-injected group, it is possible to surmise the potential danger of damage to the BBB structure of the tested vaccine. For example, if TJ mRNA levels of vaccine-injected group are significantly higher than those of the LPS-injected group 4 h after injection, one should consider the vaccine to be unsafe to BBB structure or function at the injected concentration. Further testing may be done at other concentrations.