Dataset Information

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.

ABSTRACT: 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. CONCLUSIONS:The background genomic information allowed us for the first time to follow the BCG diversity starting from the freeze-dried seed lots to descendant clinical isolates. Sequence variations in several genes of seed lot 361 did not alter the genomic stability and viability of the vaccine and appeared accumulated in isolates during the survival in the human organism. The impact of the observed variations in the context of association with the development of BCG-induced disease should be evaluated in parallel with the immune status and host genetics. Comparative genomic studies of BCG seed lots and their descendant clinical isolates represent a beneficial approach to better understand the molecular bases of efficacy and adverse events during the long-term survival of BCG in the host organism.

SUBMITTER: Narvskaya O

PROVIDER: S-EPMC7437937 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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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.

Narvskaya Olga O Starkova Daria D Levi Diana D Alexandrova Natalia N Molchanov Vladimir V Chernyaeva Ekaterina E Vyazovaya Anna A Mushkin Alexander A Zhuravlev Viacheslav V Solovieva Natalia N Vishnevskiy Boris B Mokrousov Igor I

BMC genomics 20200818 1

<h4>Background</h4>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 variati ...[more]

PMID: 32811436

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Project description:Imports of seeds for sowing are a major pathway for the introduction of contaminant seeds, and many agricultural weeds globally naturalised originally have entered through this pathway. Effective management of this pathway is a significant means of reducing future plant introductions and helps minimise agricultural losses. Using a national border inspection database, we examined the frequency, origin and identity of contaminant seeds within seed for sowing shipments entering New Zealand between 2014-2018. Our analysis looked at 41,610 seed lots across 1,420 crop seed species from over 90 countries. Overall, contamination was rare, occurring in 1.9% of all seed lots. Among the different crop types, the arable category had the lowest percentage of seed lots contaminated (0.5%) and the forage category had the highest (12.6%). Crop seeds Capsicum, Phaseolus and Solanum had the lowest contamination rates (0.0%). Forage crops Medicago (27.3%) and Trifolium (19.8%) had the highest contamination rates. Out of 191 genera recorded as contaminants, Chenopodium was the most common. Regulated quarantine weeds were the rarest contaminant type, only occurring in 0.06% of seed lots. Sorghum halepense was the most common quarantine species and was only found in vegetable seed lots. Vegetable crop seed lots accounted for approximately half of all quarantine species detections, Raphanus sativus being the most contaminated vegetable crop. Larger seed lots were significantly more contaminated and more likely to contain a quarantine species than smaller seed lots. These findings support International Seed Testing Association rules on maximum seed lot weights. Low contamination rates suggest industry practices are effective in minimising contaminant seeds. Considering New Zealand inspects every imported seed lot, utilises a working sample size 5 times larger than International Seed Testing Association rules require, trades crop seed with approximately half of the world's countries and imports thousands of crop seed species, our study provides a unique overview of contaminant seeds that move throughout the seed for sowing system.

Dataset Information

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.

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.

Similar Datasets

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