Comparative analysis of genome-wide sequences of the seed lot of the vaccine strain of Mycobacterium bovis BCG-1 (Russia) and daughter isolates obtained from children with BCG osteitis

Abstract

The objective of the study: a comparative analysis of genome-wide sequences of seed lot (SL) 361 "sh" M. bovis BCG-1 (Russia) and its daughter isolates obtained from children with manifestations of BCG osteitis.Subjects and methods: genotyping; bioinformational analysis of genome-wide sequences of PS 361 "sh” vaccine BCG-1 (Russia) and its daughter isolates.Results. PS 361 "sh" BCG-1 (Russia) was heterogeneous in 7 coding sequences with different ratios of single nucleotide substitutions inherited by 2 of 6 daughter BCG isolates. At the same time, polymorphisms did not violate the genomic stability and viability of the BCG vaccine during long-term existence in vivo. In isolates of BCG 2925 and 5448, accumulation (hypothetically, under the pressure of selection in the vaccinated organism) of nonsynonymous substitutions in 4 out of 7 polymorphic genes was noted, including the genes ppsC, eccD5, and eccA5 associated with mycobacterial virulence. Evaluation of the significance of genomic variations in BCG isolates relating to the association with the development of post-vaccination osteitis requires more detailed information about the immune status of patients. Genome-wide analysis of production strains, seed lots, finished vaccine lots and daughter clinical isolates makes the contemporary approach to understanding the molecular basis of the efficacy and complications of BCG vaccination.