Whole-Genome Sequence of Mycobacterium bovis BCG-1 (Russia)

Ludannyy, R.I.; Figueroa, Maria Alvarez; Levi, Diana; Markelov, Mikhail L.; Dedkov, Vladimir G.; Александрова, Н. В.; Shipulin, German A.

doi:10.1128/genomea.01320-15

Cited by 7 publications

(10 citation statements)

References 13 publications

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“…The G variant was previously reported in the glnD in BCG-1 (Russia) current seed lot 368 and some earlier vaccine products [ 35 ], though alternative variant A was detected in two other BCG-1 (Russia) 368 complete genomes [ 13 , 36 ]. The stability of variant A in the glnD gene of the BCG-1 (Russia) 368 working seed lot (GenBank: CP013741) and consistent vaccine batches within 2 years was confirmed by WGS [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 90%

“…Gray-scale small boxes depict sequence variants in genes related to particular proteins (proportions shown in parentheses) in seed lots 361, 367, 368, and their progeny clinical isolates. See Table 1 for more details previously sequenced complete genomes of BCG-1 (Russia) [13,35,36] along with other hyperconserved BCG strains [33].…”

Section: Discussionmentioning

confidence: 99%

“…Since 2006, the 368 ("shch") generation of M. bovis BCG-1 (Russia) strain no. 700001 is in use for the production of the BCG vaccine in Russia [12,13]. The same BCG generation 368 is also adopted by two manufacturers in India for vaccine production and distribution worldwide under the name "BCG Russia 368" [14].…”

Section: Introductionmentioning

confidence: 99%

“…The complete genome sequences of the current M. bovis BCG-1 (Russia) 368 (“shch”) freeze-dried seed lot and its working seed lot used for vaccine production by one of the Russian manufacturers are available in GenBank (NCBI) under accession numbers CP011455 [ 13 ], CP009243 [ 35 ], and CP013741 [ 36 ]. The genome constancy of M. bovis BCG-1 (Russia) 368 within the entire vaccine production flow (from working seed lot, the last production passage to final vaccine product) was confirmed by spoligotyping, 24 loci VNTR-typing, and WGS [ 36 , 37 ].…”

Section: Introductionmentioning

confidence: 99%

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First insight into the whole-genome sequence variations in Mycobacterium bovis BCG-1 (Russia) vaccine seed lots and their progeny clinical isolates from children with BCG-induced adverse events

et al. 2020

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Background: The only licensed live Bacille Calmette-Guérin (BCG) vaccine used to prevent severe childhood tuberculosis comprises genetically divergent strains with variable protective efficacy and rates of BCG-induced adverse events. The whole-genome sequencing (WGS) allowed evaluating the genome stability of BCG strains and the impact of spontaneous heterogeneity in seed and commercial lots on the efficacy of BCG-vaccines in different countries. Our study aimed to assess sequence variations and their putative effects on genes and protein functions in the BCG-1 (Russia) seed lots compared to their progeny isolates available from immunocompetent children with BCG-induced disease (mainly, osteitis). Results: Based on the WGS data, we analyzed the links between seed lots 361, 367, and 368 used for vaccine manufacture in Russia in different periods, and their nine progeny isolates recovered from immunocompetent children with BCG-induced disease. The complete catalog of variants in genes relative to the reference genome (GenBank: CP013741) included 4 synonymous and 8 nonsynonymous single nucleotide polymorphisms, and 3 frameshift deletions. Seed lot 361 shared variants with 2 of 6 descendant isolates that had higher proportions of such polymorphisms in several genes, including ppsC, eccD5, and eccA5 involved in metabolism and cell wall processes and reportedly associated with virulence in mycobacteria. One isolate preserved variants of its parent seed lot 361 without gain of further changes in the sequence profile within 14 years.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

First insight into the whole-genome sequence variations in Mycobacterium bovis BCG-1 (Russia) vaccine seed lots and their progeny clinical isolates from children with BCG-induced adverse events

et al. 2020

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“…In addition, quality control requirements comprising molecular genetic characterization of final lots and working seeds of BCG vaccines were suggested [2]. Russian research laboratories performed whole genome sequencing (WGS) of BCG Russia sub-strain genome as WHO and good manufacturing practice (GMP) recommended [3][4][5]. Currently, ten whole genome sequences of BCG sub-strains including BCG Russia are available in GenBank.…”

Section: Introductionmentioning

confidence: 99%

Mosaic Structure as the Main Feature of Mycobacterium bovis BCG Genomes

Lvovna¹,

Ivanovna²,

Sergeevna³

et al. 2018

Mycobacterium - Research and Development

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Background: The genome stability of attenuated live BCG vaccine preventing the acute forms of childhood tuberculosis is an important aspect of vaccine production. The purpose of our study was a whole genome comparative analysis of BCG sub-strains and identification of potential triggers of sub-strains' transition. Results: Genomes of three BCG Russia seed lots (1963, 1982, 2006 years) have been sequenced, and the stability of vaccine sub-strain genomes has been confirmed. A comparative genome analysis of nine Mycobacterium bovis BCG and three M. bovis strains revealed their specific genome features associated with prophage profiles. A number of prophage-coded homologs to Caudovirales ORFs were common to all BCG genomes. Prophage profiles of BCG Tice and BCG Montreal genomes were unique and coded homologs to herpes viruses ORFs. The data of phylogenetic analysis of BCG sub-strain groups based on whole genome sequences and genome restriction maps were in congruence with prophage profiles. The only fragmentary similarity of specific prophage sequences of BCG Tice, BCG Montreal, and BCG Russia 368 in pair-wise alignments was observed, suggesting the impact of prophages on mosaic structure of genomes. Conclusions: The whole genome sequencing approach is essential for genomes with mosaic structure, harboring numerous prophage sequences. Tools for prophage search are effective instruments in this analysis.

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Mapping the phylogeny and lineage history of geographically distinct BCG vaccine strains

et al. 2023

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The bacillus Calmette–Guérin (BCG) vaccine has been in use for prevention of tuberculosis for over a century. It remains the only widely available tuberculosis vaccine and its protective efficacy has varied across geographical regions. Since it was developed, the BCG vaccine strain has been shared across different laboratories around the world, where use of differing culture methods has resulted in genetically distinct strains over time. Whilst differing BCG vaccine efficacy around the world is well documented, and the reasons for this may be multifactorial, it has been hypothesized that genetic differences in BCG vaccine strains contribute to this variation. Isolates from an historic archive of lyophilized BCG strains were regrown, DNA was extracted and then whole-genome sequenced using Oxford Nanopore Technologies. The resulting whole-genome data were plotted on a phylogenetic tree and analysed to identify the presence or absence of regions of difference (RDs) and single-nucleotide polymorphisms (SNPs) relating to virulence, growth and cell wall structure. Of 50 strains available, 36 were revived in culture and 39 were sequenced. Morphology differed between the strains distributed before and after 1934. There was phylogenetic association amongst certain geographically classified strains, most notably BCG-Russia, BCG-Japan and BCG-Danish. RD2, RD171 and RD713 deletions were associated with late strains (seeded after 1927). When mapped to BCG-Pasteur 1172, the SNPs in sigK, plaA, mmaA3 and eccC5 were associated with early strains. Whilst BCG-Russia, BCG-Japan and BCG-Danish showed strong geographical isolate clustering, the late strains, including BCG-Pasteur, showed more variation. A wide range of SNPs were seen within geographically classified strains, and as much intra-strain variation as between-strain variation was seen. The date of distribution from the original Pasteur laboratory (early pre-1927 or late post-1927) gave the strongest association with genetic differences in regions of difference and virulence-related SNPs, which agrees with the previous literature.

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Whole-Genome Sequence of Mycobacterium bovis BCG-1 (Russia)

Cited by 7 publications

References 13 publications

First insight into the whole-genome sequence variations in Mycobacterium bovis BCG-1 (Russia) vaccine seed lots and their progeny clinical isolates from children with BCG-induced adverse events

First insight into the whole-genome sequence variations in Mycobacterium bovis BCG-1 (Russia) vaccine seed lots and their progeny clinical isolates from children with BCG-induced adverse events

Mosaic Structure as the Main Feature of Mycobacterium bovis BCG Genomes

Mapping the phylogeny and lineage history of geographically distinct BCG vaccine strains

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