Historical review of BCG vaccine in Japan.

Bacillus Calmette and Guérin (BCG) was introduced to Japan in 1924 by Kiyoshi Shiga and has been propagated for research purposes ever since propagation is accomplished using a glycerin-bile-potato mixture in the same manner used by Calmette and Guérin. To prepare a stable and safe freeze-dried BCG vaccine, several joint research projects were organized in 1949. At the National Institute of Infectious Diseases (formerly the National Institute of Health), the 172nd passage of BCG from the first culture was freeze-dried in 1961 and was used as the origin of the Japanese BCG strain, Tokyo-172. The Tokyo-172 was registered as an International Reference Strain in 1965 by the World Health Organization. In 1967, a multiple puncture method for BCG vaccination using a plastic cylinder implanted with nine fine needles at one end was introduced to Japan; thereafter, percutaneous administration replaced intradermal injection. The efficacy and adverse reactions of BCG vaccines as well as recent knowledge on the genetic characterization of BCG is also discussed.