The effect of passages during Japanese BCG vaccine production on genetic stability and protective efficacy.
Many genetic differences have been found among currently available BCG vaccines. To avoid continued accumulation of phenotypic or genotypic changes in the strains, WHO and most national regulatory authorities request that the vaccine should not be prepared by more than 12 passages from the master seed lot. However, it has recently been reported that genetic changes occur even during the passage for vaccine production. In this study, the genetic stability of Japanese BCG vaccine production using currently available PCR methods and protective efficacy using a guinea-pig model during the passages were examined. The results showed that there were no significant differences between the seed lot, the product manufactured by normal procedures, and the 20th passage product. These results indicate that the maximum number of passages as currently required by WHO for BCG vaccine production is adequate for the Japanese vaccine, and that new genetic tools may help to examine the quality control of the BCG vaccine.
Japan BCG Laboratory, Japan. seki@bcg.gr.jp
Masaaki
M
Seki
Tadashi
T
Udagawa
Isamu
I
Sugawara
Kenji
K
Iwama
Ikuro
I
Honda
Isao
I
Fujita
Akira
A
Hashimoto
Ikuya
I
Yano
Saburo
S
Yamamoto
D000818:Animals; D001500:BCG Vaccine / Q000235:genetics* / Q000276:immunology*; D058491:Bacterial Load; D004269:DNA, Bacterial / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D042822:Genomic Instability; D006168:Guinea Pigs; D006801:Humans; D007564:Japan; D008168:Lung / Q000382:microbiology; D009163:Mycobacterium bovis / Q000235:genetics* / Q000254:growth & development*; D016133:Polymerase Chain Reaction; D012692:Serial Passage; D014376:Tuberculosis / Q000517:prevention & control
D001500:BCG Vaccine; D004269:DNA, Bacterial