Search

Despite numerous scientific advances and dozens of alternative vaccine strategies, BCG vaccine remains the only vaccine for tuberculosis prevention, and in 2021 we have honored 100 years since its first and successful implementation. Until 2021 it is the most used vaccine in the world, with almost 4 billion doses administered. Bulgaria is one of the pioneers in the manufacture and introduction of BCG vaccine in the world, and this production has been maintained for more than 70 years. Thanks to the dedicated work of generations of specialists, the BCG vaccine gained international recognition, and in 1991, the Bulgarian BCG manufacturer was requalified by WHO as a main supplier for United Nations. The vaccine is exported and used in more than 100 countries around the world. In 2010 it was approved by WHO as an International Reference Standard. In addition to its well-established immunobiological properties, the Bulgarian BCG has also been characterized as genetically stable. Phylogenetically, the Bulgarian vaccine strain belongs to the group of early BCG strains and possesses the genetic features inherent only to the strains closest to Calmette and Guérin‘s original. In this paper we report the assembled circular genome sequence of Mycobacterium bovis BCG-Sofia SL222 and phylogeny analysis with the most closely related BCG substrains. The full circular genome of BCG-Sofia SL222 had a length of 4,370,706 bp with an average GC content of 65.60%. After 50 years of in-vitro evolution in a freeze-dried condition, we identified only four SNP mutations compared to its progenitor BCG-Russia. The availability of the complete reference genome sequence for M. bovis BCG-Sofia SL222 proves the identity of the substrain and its genetic stability, contributes to the manufacturing consistency, and has an important value in standardization and differentiation of sub-strains used in vaccine production. [ABSTRACT FROM AUTHOR]