Mutation and Pathogenicity Experiments With B C G.

Dreyer, Georges; Vollum, R. L.

doi:10.1016/s0140-6736(00)40633-1

Cited by 20 publications

(6 citation statements)

References 2 publications

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“…1). The distinction between early strains and late strains coincides with reports of ongoing attenuation of BCG in the late 1920s (6,7) and is correlated with severely reduced production of the antigenic proteins MPB70, MPB83, and MPB64 in late strains (8). However, whether this historical distinction is critical for BCG phenotypes remains uncertain, because certain properties, such as production of virulence lipids, have been independently lost in both early and late strains.…”

Section: History Of Bcg Substrainssupporting

confidence: 78%

BCG Vaccines

Tran

Liu

Behr³

2014

Microbiol Spectr

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BCG is the collective name for a family of live attenuated strains of Mycobacterium bovis that are currently used as the only vaccine against tuberculosis (TB). There are two major reasons for studying the genome of these organisms: (i) Because they are attenuated, BCG vaccines provide a window into Mycobacterium tuberculosis virulence, and (ii) because they have provided protection in several clinical trials and case-control studies, BCG vaccines may shed light on properties required of a TB vaccine. Since the determination of the M. tuberculosis genome in 1998, the study of BCG vaccines has accelerated dramatically, offering data on the genomic differences between virulent M. tuberculosis, M. bovis, and the vaccine strains. While these findings have been rewarding for the study of virulence, there is unfortunately less accrued knowledge about protection. In this chapter, we review briefly the history of BCG vaccines and then touch upon studies over the past two decades that help explain how BCG underwent attenuation, concluding with some more speculative comments as to how these vaccines might offer protection against TB.

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Section: History Of Bcg Substrainssupporting

confidence: 78%

BCG Vaccines

Tran

Liu

Behr³

2014

Microbiol Spectr

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“…8.1). The distinction between early strains and late strains coincides with reports of ongoing attenuation of BCG in the late 1920s (Dreyer and Vollum 1931), and is correlated with severely reduced production of the antigenic proteins MPB70, MPB83 and MPB64 in late strains (Milstien and Gibson 1990;Wiker et al 1996). However, whether this historical distinction is critical for BCG phenotypes remains uncertain, as certain properties such as production of virulence lipids, have been inde-pendently lost in both early and late strains (Chen et al 2007).…”

Section: Historical Aspects Of Bcgsupporting

confidence: 75%

Evolution and Strain Variation in BCG

Abdallah

Behr

2017

Advances in Experimental Medicine and Biology

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BCG vaccines were derived by in vitro passage, during the years 1908-1921, at the Pasteur Institute of Lille. Following the distribution of stocks of BCG to vaccine production laboratories around the world, it was only a few decades before different BCG producers recognized that there were variants of BCG, likely due to different passaging conditions in the different laboratories. This ultimately led to the lyophilization of stable BCG products in the 1950s and 1960s, but not before considerable evolution of the different BCG strains had taken place. The application of contemporary research methodologies has now revealed genomic, transcriptomic and proteomic differences between BCG strains. These molecular differences in part account for phenotypic differences in vitro between BCG strains, such as their variable secretion of antigenic proteins. Yet, the relevance of BCG variability for immunization policy remains elusive. In this chapter we present an overview of what is known about BCG evolution and its resulting strain variability, and provide some speculation as to the potential relevance for a vaccine given to over 100 million newborns each year.

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“…During the original derivation between 1908 and 1921, RD1 was lost and concurrently Calmette described an attenuation of virulence for animals (22). Later, between 1927 and 193 1, RD2 was lost and various investigators reported decreased vaccine lesions in humans (23) and reduced virulence in animals (24). As a basis for speculation on the impact of RD14 in humans, one can compare descriptions from the vaccine trials using BCG-Pasteur before and after this deletion.…”

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confidence: 99%

Comparative Genomics of BCG Vaccines by Whole-Genome DNA Microarray

Behr

Wilson

Gill

et al. 1999

Science

1,398

1,021

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Bacille Calmette-Guérin (BCG) vaccines are live attenuated strains of Mycobacterium bovis administered to prevent tuberculosis. To better understand the differences between M. tuberculosis, M. bovis, and the various BCG daughter strains, their genomic compositions were studied by performing comparative hybridization experiments on a DNA microarray. Regions deleted from BCG vaccines relative to the virulent M. tuberculosis H37Rv reference strain were confirmed by sequencing across the missing segment of the H37Rv genome. Eleven regions (encompassing 91 open reading frames) of H37Rv were found that were absent from one or more virulent strains of M. bovis. Five additional regions representing 38 open reading frames were present in M. bovis but absent from some or all BCG strains; this is evidence for the ongoing evolution of BCG strains since their original derivation. A precise understanding of the genetic differences between closely related Mycobacteria suggests rational approaches to the design of improved diagnostics and vaccines.

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Mutation and Pathogenicity Experiments With B C G.

Cited by 20 publications

References 2 publications

BCG Vaccines

BCG Vaccines

Evolution and Strain Variation in BCG

Comparative Genomics of BCG Vaccines by Whole-Genome DNA Microarray

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