TUBERCULIN RESPONSE AND SCAR FORMATION IN BCG VACCINATED 7-YEARS OLD SCHOOLCHILDREN IN SOFIA, BULGARIA

This study has been designed to evaluate safety and efficacy of BCG vaccine in school-entering children in terms of tuberculin response to PPD and scar formation as indicators for successful vaccination. 12 BCG lots were used to immunize 1054 tuberculin-negative children at age of 7 years. Local lesions were observed and recorded 1, 3 and 12 months after immunization, and tuberculin sensitivity was measured 3 months after BCG re-immunization. The mean diameter of local reaction was 5.58±1.63 mm at 1st month, 5.13±1.56 mm at 3rd month and 4.16±1.21 mm at 12th month respectively. Tuberculin conversion was 100% and the mean diameter of induration 3 months after BCG application was 10.53±1.66 mm. All of the results obtained pointed to the fact that Bulgarian BCG vaccine induces adequate tuberculin sensitivity to a low dose of PPD tuberculin without great local skin lesions and without occurrence of any untoward vaccination reactions. Very good consistency from batch to batch is observed and this is a proof that biological activity of the Bulgarian BCG strain is kept under continuous contro

Complete Genome Sequence, Genome Stability and Phylogeny of the Vaccine Strain Mycobacterium bovis BCG SL222 Sofia

Mycobacterium bovis bacillus Calmette–Guérin (BCG) is the only live attenuated vaccine available against tuberculosis. The first BCG vaccination was done exactly 100 years ago, in 1921. The BCG vaccine strains used worldwide represent a family of daughter sub-strains with distinct genotypic characteristics. BCG SL222 Sofia is a seed lot sub-strain descending from the Russian BCG-I (seed lot 374a) strain and has been used for vaccine production in Bulgaria since 1972. Here, we report the assembled circular genome sequence of Mycobacterium bovis BCG SL222 Sofia and phylogeny analysis with the most closely related BCG sub-strains. The full circular genome of BCG SL222 Sofia had a length of 4,370,706 bp with an average GC content of 65.60%. After 49 years of in vitro evolution in a freeze-dried condition, we identified four SNP mutations as compared to the reference BCG-I (Russia-368) sequence. BCG vaccination is of central importance for the TB elimination programs in many countries. Since 1991, almost 40 million vaccine doses of the BCG SL222 Sofia have been distributed annually through the United Nations Children’s Fund (UNICEF) and the Pan American Health Organization (PAHO) to approximately 120 countries. The availability of the complete reference genome sequence for M. bovis BCG SL222 Sofia, a WHO reference reagent for the Russian BCG-I sub-strain, will facilitate the identity assurance of the genomic stability, will contribute to more consistent manufacturing, and has an important value in standardization and differentiation of sub-strains used in vaccine production. We propose to rename the sub-strain BCG SL222 Sofia to BCG-Sofia for practical and common use